An Investigational Immuno-Therapy Study of Experimental Medication BMS-986178 by Itself or in Combination With Nivolumab and/or Ipilimumab in Participants With Solid Cancers That Are Advanced or Have Spread
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT02737475
Collaborator
(none)
166
22
9
52.5
7.5
0.1
Study Details
Study Description
Brief Summary
The purpose of the study is to determine the safety and tumor-shrinking ability of experimental medication BMS-986178, when given by itself or in combination with Nivolumab and/or Ipilimumab, in participants with solid cancers that are advanced or have spread.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
166 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2a Study of BMS-986178 Administered Alone or in Combination With Nivolumab and/or Ipilimumab in Subjects With Advanced Solid Tumors
Actual Study Start Date
:
Jun 17, 2016
Actual Primary Completion Date
:
Nov 2, 2020
Actual Study Completion Date
:
Nov 2, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: Dose Escalation BMS-986178 at specified doses at specified intervals Enrollment is closed for this arm |
Drug: BMS-986178
Specified dose on specified days
|
| Experimental: Part 2: Dose Escalation and Expansion BMS-986178 in combination with Nivolumab at specified doses at specified intervals Enrollment is closed for this arm |
Drug: BMS-986178
Specified dose on specified days
Drug: Nivolumab
Specified dose on specified days
Other Names:
|
| Experimental: Part 3: Dose Escalation and Expansion BMS-986178 in combination with Ipilimumab at specified doses at specified intervals Enrollment is closed for this arm |
Drug: BMS-986178
Specified dose on specified days
Drug: Ipilimumab
Specified dose on specified days
Other Names:
|
| Experimental: Part 4: Dose Schedule and Exploration BMS-986178/Nivolumab at specified doses at specified intervals Enrollment is closed for this arm |
Drug: BMS-986178
Specified dose on specified days
Drug: Nivolumab
Specified dose on specified days
Other Names:
|
| Experimental: Part 5: Dose Schedule and Exploration BMS-986178/Ipilimumab at specified doses at specified intervals Enrollment is closed for this arm |
Drug: BMS-986178
Specified dose on specified days
Drug: Ipilimumab
Specified dose on specified days
Other Names:
|
| Experimental: Part 6: Dose Safety and Expansion BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals Enrollment is closed for this arm |
Drug: BMS-986178
Specified dose on specified days
Drug: Nivolumab
Specified dose on specified days
Other Names:
Drug: Ipilimumab
Specified dose on specified days
Other Names:
|
| Experimental: Part 7: Dose Safety and Expansion BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals Enrollment is closed for this arm |
Drug: BMS-986178
Specified dose on specified days
Drug: Nivolumab
Specified dose on specified days
Other Names:
Drug: Ipilimumab
Specified dose on specified days
Other Names:
|
| Experimental: Part 8: Dose Exploration BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval Enrollment is closed for this arm |
Drug: BMS-986178
Specified dose on specified days
Drug: Nivolumab
Specified dose on specified days
Other Names:
Biological: Tetanus vaccine
Specified dose on specified days
|
| Experimental: Part 9: Dose Exploration BMS-986178/Nivolumab/DPV-001 vaccine/cyclophosphamide (cohort 1) at specified doses at specified intervals OR Nivolumab/DPV-001 vaccine/cyclophosphamide (cohort 2) at specified doses at specified intervals Enrollment is open for this arm [Tumor type triple negative breast cancer (TNBC)] |
Drug: BMS-986178
Specified dose on specified days
Drug: Nivolumab
Specified dose on specified days
Other Names:
Biological: DPV-001 vaccine
DPV-001 (UbiLT3 and UbiLT6): Specified dose on specified days
Drug: Cyclophosphamide
Specified dose on specified days
|
Outcome Measures
Primary Outcome Measures
- The Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) [From first dose to 28 days after first dose]
The number of participants experiencing dose-limiting toxicities (DLTs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. DLTs are defined based on the incidence, severity, and duration of adverse events (AEs) for which no clear alternative cause is identified. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
- The Number of Participants Experiencing Adverse Events (AEs) [From first dose to 100 days after last dose (up to approximately 2.5 years)]
The number of participants experiencing adverse events (AEs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
- The Number of Participants Experiencing Serious Adverse Events (SAEs) [From first dose to 100 days after last dose (up to approximately 2.5 years)]
The number of participants experiencing serious adverse events (SAEs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. A SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or is an important medical event.
- The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation [From first dose to 100 days after last dose (up to approximately 2.5 years)]
The number of participants experiencing adverse events (AEs) leading to discontinuation of study drug to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
- The Number of Participant Deaths [From first dose to study completion (up to approximately 4 years 5 months)]
The number of deaths in each arm to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors.
- The Number of Participants With Clinical Laboratory Test Abnormalities (Hematology) [From baseline to 100 days after last dose (up to approximately 2.5 years)]
The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time
- The Number of Participants With Clinical Laboratory Test Abnormalities (LIVER AND KIDNEY FUNCTION) [From baseline to 100 days after last dose (up to approximately 2.5 years)]
The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time
- The Number of Participants With Clinical Laboratory Test Abnormalities (OTHER CHEMISTRY TESTING ) [From baseline to 100 days after last dose (up to approximately 2.5 years)]
The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time
Secondary Outcome Measures
- Objective Response Rate (ORR) [From baseline up to approximately 2.5 years]
The total number of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR) based on assessment of tumor response using RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Overall Response (OR) = CR + PR Baseline is defined as the last non-missing measurement prior to the first dosing date and time.
- Duration of Response (DOR) [From baseline up to approximately 2.5 years]
The time between the date of first response and the subsequent date of disease progression or death (death after re-treatment will not be considered), whichever occurs first in participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Best overall response (BOR) is assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Baseline is defined as the last non-missing measurement prior to the first dosing date and time. Due to high percentage of censored response, median estimate may be misleading
- Progression Free Survival (PFS) Rate at 24 Weeks [24 weeks after first dose]
The percentage of treated participants remaining progression free and surviving at 24 weeks since the first dosing date.
- Cmax: Maximum Observed Serum Concentration [Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)]
The maximum observed serum concentration was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
- Tmax: Time of Maximum Observed Serum Concentration [Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)]
The time of maximum observed serum concentration was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab
- AUC(0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t [Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)]
The area under the serum concentration-time curve from time 0 to time t was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
- AUC(TAU): Area Under the Serum Concentration-time Curve in 1 Dosing Interval [Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)]
The area under the serum concentration-time curve in 1 dosing interval was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
- Ctau: Observed Serum Concentration at the End of a Dosing Interval When Intensive Samples Are Collected [Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)]
The observed serum concentration at the end of a dosing interval when intensive samples are collected was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
- CLT: Total Body Clearance [Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)]
The total body clearance was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
- Css-avg: Average Concentration Over a Dosing Interval (AUC(TAU)/Tau) [Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)]
The average concentration over a dosing interval (AUC(TAU)/tau) was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
- AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (Cmax) [Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)]
The ratio of an exposure measure at steady state to that after the first dose was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
- AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (AUC) [Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)]
The ratio of an exposure measure at steady state to that after the first dose was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
- AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (Ctau) [Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)]
The ratio of an exposure measure at steady state to that after the first dose was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
- T-HALFeff: Effective Elimination Half-life That Explains the Degree of Accumulation Observed for a Specific Exposure Measure (Exposure Measure Includes AUC(TAU), Cmax) [Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)]
The effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab
- Ctrough: Trough Observed Plasma Concentration [Cycle 1-17 timepoints can include (Pre-dose, 336, 504, 672 hours post dose)]
Trough observed plasma concentration (this includes predose concentrations and Ctau concentrations) was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
- Frequency of Positive Anti-Drug Antibodies (ADA) to BMS-986178 [Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose)]
The number of participants with positive anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of BMS-986178 administered alone or in combination with nivolumab and/or ipilimumab. ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment.
- Frequency of Positive Anti-Drug Antibodies (ADA) to Nivolumab [Cycle 1-6 timepoints can include (Pre-dose, 336, 696 hours post dose)]
The number of participants with positive anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of Nivolumab administered with BMS-986178 ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment.
- Frequency of Positive Anti-Drug Antibodies (ADA) to Ipilimumab. [Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose)]
The number of participants with positive anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of Ipilimumab administered with BMS-986178 ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment.
- The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8 [Cycle 1-6 timepoints can include (Pre-dose, 24, 168, 336, 672, 1848 hours post dose)]
The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8. A threshold of 80% receptor occupancy following treatment was applied.
- Tumor Pharmacodynamics of BMS-986178 in Combination With Nivolumab or Nivolumab Monotherapy in Part 8 [Screening, cycle 1-2 timepoints can include (Pre-dose, 336, 1848 hours post dose)]
Tumor pharmacodynamics of BMS-986178 in combination with nivolumab or nivolumab monotherapy
- The Number of Participants With Sustained T Cell Expansion With DPV-001 in Combination With Nivolumab or Nivolumab Monotherapy in Part 9 [Cycle 1-6 timepoints can include (Pre-dose, 24, 168, 336, 672, 1848 hours post dose)]
The number of participants with Sustained T Cell Expansion with DPV-001 in Combination with Nivolumab or Nivolumab Monotherapy was assessed to show a change in pharmacodynamics biomarkers
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria:
For Part 9 (only arm open for enrollment):
-
Stage IV metastatic or unresectable triple negative breast cancer (TNBC) with zero or one prior systemic therapies in the advanced metastatic setting
-
Participants with < 12 months from receipt of last curative-intent chemotherapy are allowed; curative chemotherapy will be considered first-line therapy
-
Prior receipt of chemotherapy in the (neo)adjuvant setting is acceptable, as long as completed greater than 6 months from start of treatment
-
Tumor biopsy samples (mandatory pre- and on-treatment biopsies) are required for all participants enrolled
-
Must have histologic or cytologic confirmation of a malignancy that is advanced (metastatic, recurrent, refractory, and/or unresectable) with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
-
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
-
Men and women must agree to follow specific methods of contraception, if applicable
Exclusion Criteria:
-
Must be immunotherapy treatment naïve, including no prior therapy with T cell immune checkpoint blocker (anti-PDL1, anti-PD1). Prior receipt of intralymphatic cytokine therapy (IRX-2) is acceptable (Part 9 only)
-
Other active malignancy requiring concurrent intervention
-
Prior therapy with any agent specifically targeting T-cell co-stimulation pathways such as anti-OX40 antibody, anti-CD137, anti- glucocorticoid-induced TNFR-related gene (anti-GITR) antibody, and anti-CD27
-
Known or underlying medical or psychiatric condition and/or social reason that, in the opinion of the investigator or Sponsor, could make the administration of study drug hazardous to the participant or could adversely affect the ability of the participant to comply with or tolerate the study
Other protocol-defined inclusion/exclusion criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Of Colorado | Aurora | Colorado | United States | 80045 |
| 2 | Georgetown University Medical Center | Washington | District of Columbia | United States | 20007 |
| 3 | John Theurer Cancer Center at Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 4 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 5 | Columbia University Medical Center (Cumc) | New York | New York | United States | 10032 |
| 6 | Providence Portland Medical Center | Portland | Oregon | United States | 97213 |
| 7 | Oregon Health & Science University | Portland | Oregon | United States | 97239 |
| 8 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
| 9 | Cross Cancer Institute | Edmonton | Alberta | Canada | T6G 1Z2 |
| 10 | Local Institution | Ottawa | Ontario | Canada | K1H 8L6 |
| 11 | Local Institution | Toronto | Ontario | Canada | M5G 1Z5 |
| 12 | Local Institution | Ramat Gan | Israel | 52621 | |
| 13 | Local Institution | Tel Aviv | Israel | 64239 | |
| 14 | IRCCS Istituto Nazionale Tumori Milano | Milano | Italy | 20133 | |
| 15 | Istituto Clinico Humanitas | Rozzano | Italy | 20089 | |
| 16 | Local Institution | Amsterdam | Netherlands | 1066 CX | |
| 17 | Local Institution | Utrecht | Netherlands | 3584 CX | |
| 18 | H. Univ. Vall dHebron | Barcelona | Spain | 08035 | |
| 19 | Fundacion Jimenez Diaz | Madrid | Spain | 28049 | |
| 20 | Hosp. Univ. Puerta De Hierro | Majadahonda - Madrid | Spain | 28222 | |
| 21 | Hospital Universitario Virgen De La Victoria | Malaga | Spain | 29010 | |
| 22 | Clinica Universidad de Navarra | Pamplona | Spain | 31008 |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT02737475
Other Study ID Numbers:
- CA012-004
- 2015-004816-39
First Posted:
Apr 14, 2016
Last Update Posted:
Jan 25, 2022
Last Verified:
Dec 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 165 participants were randomized and treated in Parts 1-8. 1 Participant was randomized and treated in Part 9 Cohort 1. Parts 2B, 2D, 2E, 3B, 3C, and Part 9 Cohort 2 did not enroll any participants. |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Period Title: Overall Study | |||||||||||||||||||||||||||
| STARTED | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| COMPLETED | 3 | 4 | 4 | 3 | 3 | 4 | 8 | 10 | 7 | 8 | 3 | 6 | 5 | 6 | 5 | 15 | 10 | 2 | 5 | 1 | 4 | 8 | 2 | 1 | 1 | 1 | 0 |
| NOT COMPLETED | 1 | 0 | 0 | 1 | 1 | 3 | 0 | 2 | 1 | 0 | 1 | 4 | 2 | 2 | 1 | 3 | 2 | 4 | 2 | 0 | 2 | 1 | 0 | 1 | 1 | 1 | 1 |
Baseline Characteristics
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. | Total of all reporting groups |
| Overall Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 | 166 |
| Age (Count of Participants) | ||||||||||||||||||||||||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
4
100%
|
1
25%
|
2
50%
|
1
25%
|
3
75%
|
5
71.4%
|
3
37.5%
|
10
83.3%
|
5
62.5%
|
5
62.5%
|
3
75%
|
7
70%
|
4
57.1%
|
7
87.5%
|
4
66.7%
|
8
44.4%
|
8
66.7%
|
5
83.3%
|
7
100%
|
0
0%
|
2
33.3%
|
2
22.2%
|
2
100%
|
1
50%
|
0
0%
|
0
0%
|
1
100%
|
100
60.2%
|
| >=65 years |
0
0%
|
3
75%
|
2
50%
|
3
75%
|
1
25%
|
2
28.6%
|
5
62.5%
|
2
16.7%
|
3
37.5%
|
3
37.5%
|
1
25%
|
3
30%
|
3
42.9%
|
1
12.5%
|
2
33.3%
|
10
55.6%
|
4
33.3%
|
1
16.7%
|
0
0%
|
1
100%
|
4
66.7%
|
7
77.8%
|
0
0%
|
1
50%
|
2
100%
|
2
100%
|
0
0%
|
66
39.8%
|
| Sex: Female, Male (Count of Participants) | ||||||||||||||||||||||||||||
| Female |
1
25%
|
1
25%
|
3
75%
|
1
25%
|
1
25%
|
3
42.9%
|
6
75%
|
3
25%
|
6
75%
|
2
25%
|
3
75%
|
5
50%
|
4
57.1%
|
7
87.5%
|
2
33.3%
|
1
5.6%
|
8
66.7%
|
3
50%
|
2
28.6%
|
0
0%
|
2
33.3%
|
0
0%
|
0
0%
|
1
50%
|
1
50%
|
0
0%
|
1
100%
|
67
40.4%
|
| Male |
3
75%
|
3
75%
|
1
25%
|
3
75%
|
3
75%
|
4
57.1%
|
2
25%
|
9
75%
|
2
25%
|
6
75%
|
1
25%
|
5
50%
|
3
42.9%
|
1
12.5%
|
4
66.7%
|
17
94.4%
|
4
33.3%
|
3
50%
|
5
71.4%
|
1
100%
|
4
66.7%
|
9
100%
|
2
100%
|
1
50%
|
1
50%
|
2
100%
|
0
0%
|
99
59.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||||||||||||||||||||||
| Hispanic or Latino |
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
28.6%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
6
3.6%
|
| Not Hispanic or Latino |
3
75%
|
4
100%
|
4
100%
|
3
75%
|
2
50%
|
6
85.7%
|
6
75%
|
5
41.7%
|
3
37.5%
|
3
37.5%
|
2
50%
|
7
70%
|
4
57.1%
|
4
50%
|
5
83.3%
|
6
33.3%
|
5
41.7%
|
3
50%
|
0
0%
|
1
100%
|
4
66.7%
|
3
33.3%
|
1
50%
|
2
100%
|
1
50%
|
1
50%
|
1
100%
|
89
53.6%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
1
25%
|
2
50%
|
0
0%
|
2
25%
|
6
50%
|
5
62.5%
|
5
62.5%
|
2
50%
|
3
30%
|
1
14.3%
|
4
50%
|
1
16.7%
|
12
66.7%
|
7
58.3%
|
3
50%
|
6
85.7%
|
0
0%
|
2
33.3%
|
6
66.7%
|
1
50%
|
0
0%
|
1
50%
|
1
50%
|
0
0%
|
71
42.8%
|
| Race (NIH/OMB) (Count of Participants) | ||||||||||||||||||||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.6%
|
| Asian |
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
4
2.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
25%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
4
2.4%
|
| White |
2
50%
|
3
75%
|
4
100%
|
4
100%
|
3
75%
|
6
85.7%
|
8
100%
|
12
100%
|
8
100%
|
8
100%
|
4
100%
|
8
80%
|
7
100%
|
7
87.5%
|
6
100%
|
18
100%
|
11
91.7%
|
6
100%
|
7
100%
|
1
100%
|
5
83.3%
|
8
88.9%
|
2
100%
|
2
100%
|
2
100%
|
2
100%
|
1
100%
|
155
93.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
1.2%
|
Outcome Measures
| Title | The Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) |
|---|---|
| Description | The number of participants experiencing dose-limiting toxicities (DLTs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. DLTs are defined based on the incidence, severity, and duration of adverse events (AEs) for which no clear alternative cause is identified. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. |
| Time Frame | From first dose to 28 days after first dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
| Title | The Number of Participants Experiencing Adverse Events (AEs) |
|---|---|
| Description | The number of participants experiencing adverse events (AEs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. |
| Time Frame | From first dose to 100 days after last dose (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| Count of Participants [Participants] |
4
100%
|
4
100%
|
4
100%
|
3
75%
|
4
100%
|
7
100%
|
8
100%
|
12
100%
|
7
87.5%
|
8
100%
|
4
100%
|
10
100%
|
7
100%
|
8
100%
|
6
100%
|
18
100%
|
12
100%
|
6
100%
|
6
85.7%
|
1
100%
|
6
100%
|
9
100%
|
2
100%
|
2
100%
|
2
100%
|
2
100%
|
1
100%
|
| Title | The Number of Participants Experiencing Serious Adverse Events (SAEs) |
|---|---|
| Description | The number of participants experiencing serious adverse events (SAEs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. A SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or is an important medical event. |
| Time Frame | From first dose to 100 days after last dose (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| Count of Participants [Participants] |
3
75%
|
4
100%
|
2
50%
|
3
75%
|
3
75%
|
3
42.9%
|
6
75%
|
7
58.3%
|
4
50%
|
5
62.5%
|
2
50%
|
6
60%
|
6
85.7%
|
5
62.5%
|
2
33.3%
|
11
61.1%
|
7
58.3%
|
4
66.7%
|
4
57.1%
|
1
100%
|
6
100%
|
5
55.6%
|
0
0%
|
1
50%
|
1
50%
|
1
50%
|
1
100%
|
| Title | The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation |
|---|---|
| Description | The number of participants experiencing adverse events (AEs) leading to discontinuation of study drug to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. |
| Time Frame | From first dose to 100 days after last dose (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
2
20%
|
0
0%
|
2
25%
|
0
0%
|
0
0%
|
2
16.7%
|
0
0%
|
2
28.6%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | The Number of Participant Deaths |
|---|---|
| Description | The number of deaths in each arm to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. |
| Time Frame | From first dose to study completion (up to approximately 4 years 5 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| Count of Participants [Participants] |
4
100%
|
4
100%
|
3
75%
|
4
100%
|
4
100%
|
3
42.9%
|
7
87.5%
|
11
91.7%
|
6
75%
|
6
75%
|
4
100%
|
9
90%
|
7
100%
|
8
100%
|
2
33.3%
|
16
88.9%
|
11
91.7%
|
3
50%
|
3
42.9%
|
0
0%
|
5
83.3%
|
4
44.4%
|
2
100%
|
2
100%
|
1
50%
|
1
50%
|
1
100%
|
| Title | The Number of Participants With Clinical Laboratory Test Abnormalities (Hematology) |
|---|---|
| Description | The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time |
| Time Frame | From baseline to 100 days after last dose (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants with on-treatment laboratory results and CTC grade criteria available (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| HEMOGLOBIN GRADE 1 |
2
50%
|
0
0%
|
4
100%
|
1
25%
|
2
50%
|
1
14.3%
|
4
50%
|
3
25%
|
3
37.5%
|
6
75%
|
3
75%
|
4
40%
|
2
28.6%
|
5
62.5%
|
1
16.7%
|
9
50%
|
4
33.3%
|
1
16.7%
|
3
42.9%
|
1
100%
|
2
33.3%
|
7
77.8%
|
1
50%
|
1
50%
|
1
50%
|
1
50%
|
1
100%
|
| HEMOGLOBIN GRADE 2 |
1
25%
|
2
50%
|
0
0%
|
2
50%
|
1
25%
|
4
57.1%
|
2
25%
|
5
41.7%
|
2
25%
|
0
0%
|
1
25%
|
6
60%
|
3
42.9%
|
1
12.5%
|
4
66.7%
|
6
33.3%
|
5
41.7%
|
2
33.3%
|
2
28.6%
|
0
0%
|
2
33.3%
|
2
22.2%
|
1
50%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
| HEMOGLOBIN GRADE 3 |
1
25%
|
1
25%
|
0
0%
|
1
25%
|
0
0%
|
1
14.3%
|
1
12.5%
|
1
8.3%
|
2
25%
|
1
12.5%
|
0
0%
|
0
0%
|
1
14.3%
|
2
25%
|
1
16.7%
|
3
16.7%
|
1
8.3%
|
2
33.3%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
1
50%
|
0
0%
|
| PLATELET COUNT GRADE 1 |
1
25%
|
1
25%
|
1
25%
|
1
25%
|
0
0%
|
1
14.3%
|
2
25%
|
1
8.3%
|
1
12.5%
|
0
0%
|
0
0%
|
1
10%
|
2
28.6%
|
1
12.5%
|
2
33.3%
|
4
22.2%
|
3
25%
|
1
16.7%
|
1
14.3%
|
0
0%
|
1
16.7%
|
2
22.2%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
| PLATELET COUNT GRADE 2 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
| PLATELET COUNT GRADE 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| LEUKOCYTES GRADE 1 |
1
25%
|
1
25%
|
2
50%
|
0
0%
|
0
0%
|
0
0%
|
2
25%
|
1
8.3%
|
2
25%
|
1
12.5%
|
0
0%
|
1
10%
|
1
14.3%
|
3
37.5%
|
2
33.3%
|
2
11.1%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
| LEUKOCYTES GRADE 2 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
1
10%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
2
22.2%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
| LEUKOCYTES GRADE 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
1
16.7%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| LEUKOCYTES GRADE 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ABSOLUTE NEUTROPHIL COUNT DRV. GRADE 1 |
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
3
37.5%
|
0
0%
|
2
25%
|
0
0%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
0
0%
|
2
11.1%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
| ABSOLUTE NEUTROPHIL COUNT DRV. GRADE 2 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ABSOLUTE NEUTROPHIL COUNT DRV. GRADE 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ABSOLUTE NEUTROPHIL COUNT DRV. GRADE 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | The Number of Participants With Clinical Laboratory Test Abnormalities (LIVER AND KIDNEY FUNCTION) |
|---|---|
| Description | The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time |
| Time Frame | From baseline to 100 days after last dose (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants with on-treatment laboratory results and CTC grade criteria available (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| ALKALINE PHOSPHATASE GRADE 1 |
2
50%
|
2
50%
|
2
50%
|
1
25%
|
3
75%
|
5
71.4%
|
2
25%
|
5
41.7%
|
6
75%
|
4
50%
|
2
50%
|
3
30%
|
3
42.9%
|
4
50%
|
0
0%
|
7
38.9%
|
6
50%
|
2
33.3%
|
1
14.3%
|
0
0%
|
3
50%
|
2
22.2%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
1
100%
|
| ALKALINE PHOSPHATASE GRADE 2 |
1
25%
|
1
25%
|
1
25%
|
2
50%
|
0
0%
|
1
14.3%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
2
20%
|
0
0%
|
1
12.5%
|
1
16.7%
|
3
16.7%
|
1
8.3%
|
0
0%
|
1
14.3%
|
1
100%
|
1
16.7%
|
2
22.2%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
1
100%
|
| ALKALINE PHOSPHATASE GRADE 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
25%
|
2
16.7%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
1
16.7%
|
2
11.1%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
| ASPARTATE AMINOTRANSFERASE GRADE 1 |
2
50%
|
3
75%
|
1
25%
|
1
25%
|
1
25%
|
3
42.9%
|
4
50%
|
2
16.7%
|
1
12.5%
|
2
25%
|
0
0%
|
4
40%
|
2
28.6%
|
2
25%
|
2
33.3%
|
10
55.6%
|
5
41.7%
|
4
66.7%
|
3
42.9%
|
0
0%
|
5
83.3%
|
2
22.2%
|
0
0%
|
1
50%
|
1
50%
|
0
0%
|
1
100%
|
| ASPARTATE AMINOTRANSFERASE GRADE 2 |
0
0%
|
0
0%
|
1
25%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
2
33.3%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
100%
|
| ASPARTATE AMINOTRANSFERASE GRADE 3 |
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
2
25%
|
1
8.3%
|
1
12.5%
|
0
0%
|
2
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ASPARTATE AMINOTRANSFERASE GRADE 4 |
1
25%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ALANINE AMINOTRANSFERASE GRADE 1 |
1
25%
|
3
75%
|
2
50%
|
2
50%
|
0
0%
|
2
28.6%
|
4
50%
|
1
8.3%
|
2
25%
|
0
0%
|
1
25%
|
4
40%
|
1
14.3%
|
1
12.5%
|
2
33.3%
|
7
38.9%
|
4
33.3%
|
3
50%
|
1
14.3%
|
0
0%
|
3
50%
|
3
33.3%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
1
100%
|
| ALANINE AMINOTRANSFERASE GRADE 2 |
1
25%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
1
12.5%
|
1
8.3%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ALANINE AMINOTRANSFERASE GRADE 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ALANINE AMINOTRANSFERASE GRADE 4 |
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| BILIRUBIN, TOTAL GRADE 1 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
1
8.3%
|
0
0%
|
0
0%
|
1
25%
|
1
10%
|
0
0%
|
0
0%
|
0
0%
|
2
11.1%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| BILIRUBIN, TOTAL GRADE 2 |
0
0%
|
0
0%
|
0
0%
|
2
50%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
1
100%
|
| BILIRUBIN, TOTAL GRADE 3 |
1
25%
|
1
25%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| BILIRUBIN, TOTAL GRADE 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| CREATININE GRADE 1 |
2
50%
|
1
25%
|
2
50%
|
1
25%
|
0
0%
|
0
0%
|
3
37.5%
|
6
50%
|
1
12.5%
|
1
12.5%
|
0
0%
|
1
10%
|
1
14.3%
|
3
37.5%
|
2
33.3%
|
7
38.9%
|
0
0%
|
1
16.7%
|
2
28.6%
|
1
100%
|
2
33.3%
|
3
33.3%
|
1
50%
|
1
50%
|
1
50%
|
1
50%
|
0
0%
|
| CREATININE GRADE 2 |
0
0%
|
1
25%
|
0
0%
|
1
25%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
3
16.7%
|
2
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
22.2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| CREATININE GRADE 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
2
11.1%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | The Number of Participants With Clinical Laboratory Test Abnormalities (OTHER CHEMISTRY TESTING ) |
|---|---|
| Description | The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time |
| Time Frame | From baseline to 100 days after last dose (up to approximately 2.5 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants with on-treatment laboratory results and CTC grade criteria available (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| SODIUM, SERUM GRADE 1 |
4
100%
|
3
75%
|
2
50%
|
2
50%
|
1
25%
|
2
28.6%
|
6
75%
|
5
41.7%
|
2
25%
|
2
25%
|
2
50%
|
2
20%
|
2
28.6%
|
2
25%
|
2
33.3%
|
4
22.2%
|
3
25%
|
1
16.7%
|
0
0%
|
0
0%
|
4
66.7%
|
1
11.1%
|
0
0%
|
1
50%
|
0
0%
|
1
50%
|
1
100%
|
| SODIUM, SERUM GRADE 2 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| SODIUM, SERUM GRADE 3 |
0
0%
|
0
0%
|
1
25%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
2
25%
|
0
0%
|
2
11.1%
|
0
0%
|
2
33.3%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
1
100%
|
| POTASSIUM, SERUM GRADE 1 |
0
0%
|
3
75%
|
0
0%
|
2
50%
|
0
0%
|
1
14.3%
|
4
50%
|
3
25%
|
2
25%
|
2
25%
|
0
0%
|
2
20%
|
3
42.9%
|
2
25%
|
2
33.3%
|
8
44.4%
|
3
25%
|
0
0%
|
1
14.3%
|
0
0%
|
2
33.3%
|
2
22.2%
|
1
50%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
| POTASSIUM, SERUM GRADE 2 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
16.7%
|
1
8.3%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| POTASSIUM, SERUM GRADE 3 |
0
0%
|
0
0%
|
0
0%
|
1
25%
|
1
25%
|
0
0%
|
1
12.5%
|
0
0%
|
1
12.5%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
1
5.6%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| POTASSIUM, SERUM GRADE 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5.6%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| CALCIUM, TOTAL GRADE 1 |
0
0%
|
3
75%
|
1
25%
|
1
25%
|
1
25%
|
3
42.9%
|
5
62.5%
|
4
33.3%
|
2
25%
|
4
50%
|
2
50%
|
4
40%
|
3
42.9%
|
0
0%
|
2
33.3%
|
9
50%
|
4
33.3%
|
1
16.7%
|
4
57.1%
|
0
0%
|
1
16.7%
|
5
55.6%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| CALCIUM, TOTAL GRADE 2 |
1
25%
|
0
0%
|
2
50%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
3
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
1
5.6%
|
2
16.7%
|
1
16.7%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
50%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
| CALCIUM, TOTAL GRADE 3 |
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
1
5.6%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| MAGNESIUM, SERUM GRADE 1 |
1
25%
|
1
25%
|
0
0%
|
2
50%
|
2
50%
|
0
0%
|
1
12.5%
|
3
25%
|
4
50%
|
1
12.5%
|
2
50%
|
4
40%
|
0
0%
|
0
0%
|
2
33.3%
|
6
33.3%
|
2
16.7%
|
2
33.3%
|
0
0%
|
0
0%
|
3
50%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
2
100%
|
0
0%
|
| MAGNESIUM, SERUM GRADE 2 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
2
25%
|
0
0%
|
0
0%
|
2
25%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
1
5.6%
|
2
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| MAGNESIUM, SERUM GRADE 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| GLUCOSE, FASTING SERUM GRADE 1 |
1
25%
|
3
75%
|
0
0%
|
3
75%
|
1
25%
|
4
57.1%
|
4
50%
|
2
16.7%
|
2
25%
|
0
0%
|
2
50%
|
6
60%
|
5
71.4%
|
2
25%
|
2
33.3%
|
2
11.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|||||||
| GLUCOSE, FASTING SERUM GRADE 2 |
0
0%
|
0
0%
|
1
25%
|
0
0%
|
1
25%
|
0
0%
|
2
25%
|
1
8.3%
|
0
0%
|
1
12.5%
|
0
0%
|
1
10%
|
1
14.3%
|
0
0%
|
0
0%
|
1
5.6%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
|||||||
| GLUCOSE, FASTING SERUM GRADE 3 |
1
25%
|
0
0%
|
1
25%
|
0
0%
|
1
25%
|
1
14.3%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|||||||
| ALBUMIN GRADE 1 |
2
50%
|
2
50%
|
1
25%
|
2
50%
|
1
25%
|
2
28.6%
|
0
0%
|
4
33.3%
|
1
12.5%
|
3
37.5%
|
1
25%
|
2
20%
|
5
71.4%
|
2
25%
|
1
16.7%
|
3
16.7%
|
4
33.3%
|
2
33.3%
|
0
0%
|
0
0%
|
1
16.7%
|
2
22.2%
|
1
50%
|
0
0%
|
2
100%
|
1
50%
|
0
0%
|
| ALBUMIN GRADE 2 |
1
25%
|
2
50%
|
2
50%
|
1
25%
|
1
25%
|
3
42.9%
|
5
62.5%
|
3
25%
|
3
37.5%
|
0
0%
|
2
50%
|
4
40%
|
1
14.3%
|
2
25%
|
3
50%
|
5
27.8%
|
2
16.7%
|
2
33.3%
|
2
28.6%
|
1
100%
|
3
50%
|
4
44.4%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
1
100%
|
| ALBUMIN GRADE 3 |
0
0%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
| AMYLASE, TOTAL GRADE 1 |
1
25%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
1
14.3%
|
0
0%
|
3
25%
|
1
12.5%
|
0
0%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
0
0%
|
2
11.1%
|
2
16.7%
|
1
16.7%
|
1
14.3%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AMYLASE, TOTAL GRADE 2 |
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
1
12.5%
|
0
0%
|
1
25%
|
1
10%
|
1
14.3%
|
1
12.5%
|
0
0%
|
2
11.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AMYLASE, TOTAL GRADE 3 |
0
0%
|
0
0%
|
2
50%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5.6%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AMYLASE, TOTAL GRADE 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
| LIPASE, TOTAL GRADE 1 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
1
8.3%
|
1
12.5%
|
0
0%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
1
16.7%
|
2
11.1%
|
1
8.3%
|
1
16.7%
|
1
14.3%
|
1
100%
|
1
16.7%
|
2
22.2%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
| LIPASE, TOTAL GRADE 2 |
1
25%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
1
5.6%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| LIPASE, TOTAL GRADE 3 |
1
25%
|
1
25%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
2
16.7%
|
0
0%
|
1
12.5%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
0
0%
|
2
11.1%
|
1
8.3%
|
2
33.3%
|
2
28.6%
|
0
0%
|
1
16.7%
|
2
22.2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| LIPASE, TOTAL GRADE 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
11.1%
|
1
8.3%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
| Title | Objective Response Rate (ORR) |
|---|---|
| Description | The total number of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR) based on assessment of tumor response using RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Overall Response (OR) = CR + PR Baseline is defined as the last non-missing measurement prior to the first dosing date and time. |
| Time Frame | From baseline up to approximately 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response Evaluable Participants (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 9 | 8 | 8 | 5 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
25%
|
1
8.3%
|
1
12.5%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5.6%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
2
22.2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
NA
NaN
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | The time between the date of first response and the subsequent date of disease progression or death (death after re-treatment will not be considered), whichever occurs first in participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Best overall response (BOR) is assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Baseline is defined as the last non-missing measurement prior to the first dosing date and time. Due to high percentage of censored response, median estimate may be misleading |
| Time Frame | From baseline up to approximately 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of responders within each tumor type was not sufficient for analysis. (Parts 1-8) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Median (95% Confidence Interval) [Weeks] |
NA
|
17.14
|
NA
|
NA
|
NA
|
64.14
|
NA
|
| Title | Progression Free Survival (PFS) Rate at 24 Weeks |
|---|---|
| Description | The percentage of treated participants remaining progression free and surviving at 24 weeks since the first dosing date. |
| Time Frame | 24 weeks after first dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated Participants (Parts 1-8) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 |
| Number (95% Confidence Interval) [Percentage of participants] |
0.0
0%
|
0.0
0%
|
0.0
0%
|
25.0
625%
|
25.0
625%
|
17.9
255.7%
|
42.9
536.3%
|
16.7
139.2%
|
28.6
357.5%
|
37.5
468.8%
|
0.0
0%
|
11.1
111%
|
0.0
0%
|
0.0
0%
|
40.0
666.7%
|
22.2
123.3%
|
9.2
76.7%
|
0.0
0%
|
28.6
408.6%
|
NA
NaN
|
0.0
0%
|
33.3
370%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
50.0
2500%
|
| Title | Cmax: Maximum Observed Serum Concentration |
|---|---|
| Description | The maximum observed serum concentration was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead. |
| Time Frame | Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 1 DAY 1 |
4964
(11)
|
11245
(34)
|
19254
(18)
|
36143
(14)
|
68774
(20)
|
9424
(133)
|
11699
(13)
|
19547
(39)
|
39182
(37)
|
76445
(22)
|
7860
(35)
|
9345
(20)
|
17979
(31)
|
55790
(107)
|
65472
(27)
|
17586
(25)
|
19012
(22)
|
21399
(12)
|
11139
(19)
|
14267
(37)
|
15424
(173)
|
3270
(NA)
|
11300
(NA)
|
||||
| CYCLE 4 DAY 1 |
8960
(NA)
|
10273
(12)
|
20900
(NA)
|
69922
(36)
|
117839
(15)
|
31800
(NA)
|
11261
(21)
|
14143
(47)
|
|||||||||||||||||||
| CYCLE 5 DAY 1 |
16912
(36)
|
||||||||||||||||||||||||||
| CYCLE 9 DAY 1 |
23200
(NA)
|
61500
(NA)
|
17392
(19)
|
23097
(66)
|
72991
(12)
|
207853
(33)
|
30922
(30)
|
| Title | Tmax: Time of Maximum Observed Serum Concentration |
|---|---|
| Description | The time of maximum observed serum concentration was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab |
| Time Frame | Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 1 DAY 1 |
0.675
|
0.575
|
4.58
|
2.30
|
0.558
|
0.467
|
2.34
|
0.517
|
0.650
|
0.792
|
0.667
|
4.00
|
4.00
|
2.55
|
4.13
|
4.09
|
0.550
|
2.30
|
0.583
|
4.00
|
0.475
|
0.533
|
4.83
|
||||
| CYCLE 4 DAY 1 |
0.583
|
4.00
|
0.583
|
4.00
|
2.58
|
4.03
|
0.517
|
0.467
|
|||||||||||||||||||
| CYCLE 5 DAY 1 |
0.550
|
||||||||||||||||||||||||||
| CYCLE 9 DAY 1 |
0.467
|
22.7
|
0.567
|
4.47
|
2.38
|
4.05
|
3.94
|
| Title | AUC(0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t |
|---|---|
| Description | The area under the serum concentration-time curve from time 0 to time t was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead. |
| Time Frame | Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 1 DAY 1 |
577541
(31)
|
1678196
(23)
|
1825502
(61)
|
5024906
(32)
|
9981469
(9)
|
609426
(62)
|
1495494
(27)
|
2324225
(24)
|
5458640
(47)
|
8694104
(46)
|
1047354
(49)
|
1197507
(43)
|
2774058
(56)
|
7257441
(34)
|
10580541
(41)
|
2351794
(29)
|
2000522
(43)
|
3216650
(21)
|
1251698
(49)
|
1653102
(22)
|
864500
(57)
|
390424
(NA)
|
2399055
(NA)
|
||||
| CYCLE 4 DAY 1 |
773957
(NA)
|
2210404
(21)
|
2400433
(NA)
|
10729551
(38)
|
23851864
(14)
|
2699238
(NA)
|
1837861
(10)
|
504998
(91)
|
|||||||||||||||||||
| CYCLE 5 DAY 1 |
2520673
(50)
|
||||||||||||||||||||||||||
| CYCLE 9 DAY 1 |
3952990
(NA)
|
13024914
(NA)
|
2971409
(53)
|
1247687
(118)
|
16483279
(37)
|
28499982
(78)
|
4537054
(42)
|
| Title | AUC(TAU): Area Under the Serum Concentration-time Curve in 1 Dosing Interval |
|---|---|
| Description | The area under the serum concentration-time curve in 1 dosing interval was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead. |
| Time Frame | Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 1 DAY 1 |
577541
(31)
|
1599886
(29)
|
3142196
(21)
|
5854143
(19)
|
9981469
(9)
|
663257
(60)
|
1515139
(24)
|
2551115
(24)
|
5458640
(47)
|
11483961
(26)
|
1383126
(28)
|
1521223
(31)
|
3133192
(49)
|
7464248
(32)
|
11966698
(34)
|
2602049
(23)
|
2734577
(31)
|
3500606
(28)
|
1568004
(33)
|
1705864
(10)
|
1410042
(23)
|
447709
(NA)
|
2812249
(NA)
|
||||
| CYCLE 4 DAY 1 |
2210404
(21)
|
12666237
(39)
|
27936423
(8)
|
1837861
(10)
|
3590883
(12)
|
||||||||||||||||||||||
| CYCLE 5 DAY 1 |
3335668
(56)
|
||||||||||||||||||||||||||
| CYCLE 9 DAY 1 |
3952990
(NA)
|
13024914
(NA)
|
3345948
(40)
|
3307867
(83)
|
16483279
(37)
|
50254284
(42)
|
6176469
(17)
|
| Title | Ctau: Observed Serum Concentration at the End of a Dosing Interval When Intensive Samples Are Collected |
|---|---|
| Description | The observed serum concentration at the end of a dosing interval when intensive samples are collected was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead. |
| Time Frame | Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 1 DAY 1 |
657
(62)
|
2577
(30)
|
5354
(31)
|
10852
(44)
|
16514
(4)
|
756
(108)
|
1904
(37)
|
3598
(37)
|
10413
(51)
|
18596
(41)
|
885
(56)
|
604
(67)
|
2335
(87)
|
3059
(93)
|
7739
(72)
|
3928
(33)
|
544
(76)
|
1725
(76)
|
790
(88)
|
1535
(35)
|
1533
(54)
|
0.004
(NA)
|
42.9
(NA)
|
||||
| CYCLE 4 DAY 1 |
2527
(68)
|
7729
(49)
|
32982
(33)
|
1262
(10)
|
6906
(20)
|
||||||||||||||||||||||
| CYCLE 5 DAY 1 |
1412
(78)
|
||||||||||||||||||||||||||
| CYCLE 9 DAY 1 |
6470
(NA)
|
33600
(NA)
|
5510
(68)
|
5686
(78)
|
34303
(25)
|
131520
(70)
|
13400
(26)
|
| Title | CLT: Total Body Clearance |
|---|---|
| Description | The total body clearance was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead. |
| Time Frame | Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 4 DAY 1 |
0.018
(24)
|
0.013
(44)
|
0.011
(8)
|
0.022
(10)
|
0.011
(13)
|
||||||||||||||||||||||
| CYCLE 5 DAY 1 |
0.024
(56)
|
||||||||||||||||||||||||||
| CYCLE 9 DAY 1 |
0.020
(NA)
|
0.012
(NA)
|
0.012
(38)
|
0.024
(83)
|
0.010
(37)
|
0.006
(42)
|
0.013
(19)
|
| Title | Css-avg: Average Concentration Over a Dosing Interval (AUC(TAU)/Tau) |
|---|---|
| Description | The average concentration over a dosing interval (AUC(TAU)/tau) was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead. |
| Time Frame | Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 4 DAY 1 |
4379
(21)
|
25131
(39)
|
55386
(8)
|
3715
(10)
|
10739
(12)
|
||||||||||||||||||||||
| CYCLE 5 DAY 1 |
4964
(56)
|
||||||||||||||||||||||||||
| CYCLE 9 DAY 1 |
11826
(NA)
|
45155
(NA)
|
9746
(42)
|
9903
(83)
|
45878
(27)
|
148579
(42)
|
19538
(19)
|
| Title | AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (Cmax) |
|---|---|
| Description | The ratio of an exposure measure at steady state to that after the first dose was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead. |
| Time Frame | Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 4 DAY 1 |
0.793
(NA)
|
1.05
(21)
|
1.67
(NA)
|
1.40
(18)
|
1.52
(18)
|
1.32
(NA)
|
1.03
(15)
|
1.21
(43)
|
|||||||||||||||||||
| CYCLE 5 DAY 1 |
1.02
(5)
|
||||||||||||||||||||||||||
| CYCLE 9 DAY 1 |
1.45
(NA)
|
1.89
(NA)
|
1.40
(22)
|
1.29
(66)
|
1.83
(14)
|
2.56
(29)
|
1.66
(32)
|
| Title | AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (AUC) |
|---|---|
| Description | The ratio of an exposure measure at steady state to that after the first dose was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead. |
| Time Frame | Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 4 DAY 1 |
1.28
(7)
|
1.56
(19)
|
1.77
(27)
|
0.000
(NA)
|
1.37
(12)
|
2.13
(116)
|
|||||||||||||||||||||
| CYCLE 5 DAY 1 |
1.21
(34)
|
||||||||||||||||||||||||||
| CYCLE 9 DAY 1 |
2.21
(NA)
|
1.85
(24)
|
0.748
(141)
|
2.78
(34)
|
4.40
(87)
|
2.32
(9)
|
| Title | AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (Ctau) |
|---|---|
| Description | The ratio of an exposure measure at steady state to that after the first dose was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead. |
| Time Frame | Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 4 DAY 1 |
1.90
(73)
|
1.22
(16)
|
1.89
(29)
|
0.000
(NA)
|
2.47
(57)
|
2.72
(116)
|
|||||||||||||||||||||
| CYCLE 5 DAY 1 |
1.05
(48)
|
||||||||||||||||||||||||||
| CYCLE 9 DAY 1 |
2.33
(NA)
|
2.40
(36)
|
1.22
(141)
|
2.61
(11)
|
7.55
(87)
|
3.49
(11)
|
| Title | T-HALFeff: Effective Elimination Half-life That Explains the Degree of Accumulation Observed for a Specific Exposure Measure (Exposure Measure Includes AUC(TAU), Cmax) |
|---|---|
| Description | The effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab |
| Time Frame | Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 4 DAY 1 |
229
(40)
|
345
(111)
|
429
(182)
|
0.000
(NA)
|
261
(58)
|
146
(200)
|
|||||||||||||||||||||
| CYCLE 5 DAY 1 |
447
(NA)
|
||||||||||||||||||||||||||
| CYCLE 9 DAY 1 |
0.000
(NA)
|
331
(NA)
|
315
(119)
|
0.000
(0.000)
|
593
(308)
|
607
(527)
|
312
(180)
|
| Title | Ctrough: Trough Observed Plasma Concentration |
|---|---|
| Description | Trough observed plasma concentration (this includes predose concentrations and Ctau concentrations) was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead. |
| Time Frame | Cycle 1-17 timepoints can include (Pre-dose, 336, 504, 672 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic participants: All participants with available serum time-concentration data from subjects who received any BMS-986178 or Nivolumab or Ipilimumab. (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 4 | 4 | 4 | 4 | 4 | 7 | 8 | 12 | 8 | 8 | 4 | 10 | 7 | 8 | 6 | 18 | 12 | 6 | 7 | 1 | 6 | 9 | 2 | 2 | 2 | 2 | 1 |
| CYCLE 1 DAY 15 336 h |
1535
(34.9)
|
1912
(45.2)
|
|||||||||||||||||||||||||
| CYCLE 1 DAY 29 0 h |
1354
(65.0)
|
1108
(72.9)
|
|||||||||||||||||||||||||
| CYCLE 2 DAY 1 0 h |
1391
(63.3)
|
1107
(84.5)
|
|||||||||||||||||||||||||
| CYCLE 2 DAY 1 336 h |
657
(62.2)
|
2372
(38.9)
|
5354
(31.0)
|
10852
(44.3)
|
16514
(4.14)
|
561
(119)
|
1995
(35.1)
|
4006
(31.0)
|
10413
(51.3)
|
18596
(41.4)
|
4070
(30.7)
|
||||||||||||||||
| CYCLE 2 DAY 1 504 h |
456
(85.5)
|
591
(76.7)
|
2401
(86.0)
|
1921
(103)
|
7739
(72.3)
|
2166
(33.7)
|
745
(90.9)
|
1030
(NA)
|
|||||||||||||||||||
| CYCLE 2 DAY 1 672 h |
676
(105)
|
||||||||||||||||||||||||||
| CYCLE 3 DAY 1 0 h |
1290
(43.3)
|
4244
(36.2)
|
5903
(45.5)
|
16974
(28.9)
|
21571
(15.9)
|
614
(122)
|
1825
(70.1)
|
4498
(45.4)
|
16379
(43.6)
|
28282
(43.2)
|
323
(101)
|
2049
(40.1)
|
4894
(60.7)
|
2766
(99.8)
|
20410
(42.5)
|
5055
(46.8)
|
1480
(81.5)
|
62.5
(NA)
|
689
(123)
|
2469
(64.6)
|
|||||||
| CYCLE 4 DAY 1 0 h |
3420
(NA)
|
4593
(24.0)
|
7169
(37.3)
|
20703
(32.1)
|
26090
(13.0)
|
358
(95.8)
|
2095
(96.5)
|
5108
(71.4)
|
20800
(43.7)
|
47108
(45.2)
|
1080
(NA)
|
1971
(51.3)
|
5140
(NA)
|
12649
(78.3)
|
32150
(0.660)
|
7252
(43.4)
|
1466
(72.4)
|
754
(48.1)
|
5461
(26.4)
|
||||||||
| CYCLE 4 DAY 29 0 |
1856
(75.1)
|
||||||||||||||||||||||||||
| CYCLE 4 DAY 15 336 h |
2130
(69.4)
|
||||||||||||||||||||||||||
| CYCLE 5 DAY 1 0 h |
6600
(NA)
|
13491
(36.0)
|
13300
(NA)
|
35200
(NA)
|
386
(84.8)
|
1301
(100)
|
7468
(55.1)
|
26813
(52.7)
|
90700
(NA)
|
9811
(37.3)
|
1671
(63.5)
|
||||||||||||||||
| CYCLE 5 DAY 1 504 h |
2527
(67.6)
|
18771
(45.0)
|
1262
(10.2)
|
||||||||||||||||||||||||
| CYCLE 6 DAY 1 0 h |
604
(138)
|
||||||||||||||||||||||||||
| CYCLE 6 DAY 1 672 h |
62.5
(NA)
|
||||||||||||||||||||||||||
| CYCLE 7 DAY 1 0 h |
5390
(NA)
|
10217
(45.8)
|
22073
(60.3)
|
946
(NA)
|
4777
(75.6)
|
12527
(58.8)
|
32753
(53.9)
|
76970
(33.0)
|
11471
(38.5)
|
||||||||||||||||||
| CYCLE 9 DAY 1 0 h |
6300
(NA)
|
31300
(NA)
|
6397
(50.5)
|
13536
(105)
|
29902
(30.0)
|
106710
(40.9)
|
12905
(42.4)
|
579
(NA)
|
|||||||||||||||||||
| CYCLE 10 DAY 1 0 h |
29100
(NA)
|
||||||||||||||||||||||||||
| CYCLE 10 DAY 1 336 h |
6470
(NA)
|
33600
(NA)
|
1190
(NA)
|
8264
(44.0)
|
5686
(78.2)
|
28988
(33.9)
|
131520
(70.3)
|
13400
(26.3)
|
|||||||||||||||||||
| CYCLE 17 DAY 1 0 h |
48500
(NA)
|
16600
(NA)
|
| Title | Frequency of Positive Anti-Drug Antibodies (ADA) to BMS-986178 |
|---|---|
| Description | The number of participants with positive anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of BMS-986178 administered alone or in combination with nivolumab and/or ipilimumab. ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment. |
| Time Frame | Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All BMS 986178 Treated Participants with Baseline and at Least One Post-baseline ADA Assessment (Parts 1-9) |
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 1 | 2 | 3 | 3 | 3 | 6 | 6 | 6 | 7 | 5 | 2 | 5 | 6 | 7 | 6 | 0 | 2 | 0 | 0 | 0 | 0 | 3 | 1 | 1 | 0 | 0 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
3
42.9%
|
1
12.5%
|
3
25%
|
1
12.5%
|
0
0%
|
1
25%
|
3
30%
|
1
14.3%
|
4
50%
|
2
33.3%
|
1
5.6%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Frequency of Positive Anti-Drug Antibodies (ADA) to Nivolumab |
|---|---|
| Description | The number of participants with positive anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of Nivolumab administered with BMS-986178 ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment. |
| Time Frame | Cycle 1-6 timepoints can include (Pre-dose, 336, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All BMS 986178 Treated Participants with Baseline and at Least One Post-baseline ADA Assessment (Parts 1-9) |
| Arm/Group Title | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 5 | 7 | 8 | 8 | 6 | 17 | 9 | 5 | 1 | 5 | 9 | 0 | 1 | 0 | 1 | 0 |
| Count of Participants [Participants] |
0
0%
|
1
25%
|
1
25%
|
0
0%
|
0
0%
|
3
42.9%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
1
25%
|
1
10%
|
0
0%
|
| Title | Frequency of Positive Anti-Drug Antibodies (ADA) to Ipilimumab. |
|---|---|
| Description | The number of participants with positive anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of Ipilimumab administered with BMS-986178 ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment. |
| Time Frame | Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All BMS 986178 Treated Participants with Baseline and at Least One Post-baseline ADA Assessment (Parts 1-9) |
| Arm/Group Title | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. |
| Measure Participants | 4 | 5 | 7 | 7 | 6 | 6 | 6 | 1 | 5 | 9 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
1
25%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8 |
|---|---|
| Description | The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8. A threshold of 80% receptor occupancy following treatment was applied. |
| Time Frame | Cycle 1-6 timepoints can include (Pre-dose, 24, 168, 336, 672, 1848 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants with Pharmacodynamic biomarker assessments (Part 8) |
| Arm/Group Title | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W |
|---|---|---|---|---|
| Arm/Group Description | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. |
| Measure Participants | 2 | 2 | 2 | 2 |
| Peripheral OX40 receptor occupancy (CD4+ T cells) |
1
25%
|
2
50%
|
1
25%
|
0
0%
|
| Peripheral OX40 receptor occupancy (Tregs) |
1
25%
|
1
25%
|
1
25%
|
0
0%
|
| Title | Tumor Pharmacodynamics of BMS-986178 in Combination With Nivolumab or Nivolumab Monotherapy in Part 8 |
|---|---|
| Description | Tumor pharmacodynamics of BMS-986178 in combination with nivolumab or nivolumab monotherapy |
| Time Frame | Screening, cycle 1-2 timepoints can include (Pre-dose, 336, 1848 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Tumor pharmacodynamic readouts not possible due to only 1 matched pair |
| Arm/Group Title | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W |
|---|---|---|---|---|
| Arm/Group Description | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | The Number of Participants With Sustained T Cell Expansion With DPV-001 in Combination With Nivolumab or Nivolumab Monotherapy in Part 9 |
|---|---|
| Description | The number of participants with Sustained T Cell Expansion with DPV-001 in Combination with Nivolumab or Nivolumab Monotherapy was assessed to show a change in pharmacodynamics biomarkers |
| Time Frame | Cycle 1-6 timepoints can include (Pre-dose, 24, 168, 336, 672, 1848 hours post dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants with available biomarker data (Part 9) |
| Arm/Group Title | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine |
|---|---|
| Arm/Group Description | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | From first dose to 100 days post last dose (up to 2.5 years) All Cause Mortality from first dose to study completion (up to approximately 4 years 5 months) | |||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arm/Group Title | Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine | |||||||||||||||||||||||||||
| Arm/Group Description | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles. | Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles. | Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles. | Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w). | Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). | Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. | Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. | BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178. | Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. . A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy. | Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles. | |||||||||||||||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine | ||||||||||||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 4/4 (100%) | 3/4 (75%) | 4/4 (100%) | 4/4 (100%) | 3/7 (42.9%) | 7/8 (87.5%) | 11/12 (91.7%) | 6/8 (75%) | 6/8 (75%) | 4/4 (100%) | 9/10 (90%) | 7/7 (100%) | 8/8 (100%) | 2/6 (33.3%) | 16/18 (88.9%) | 11/12 (91.7%) | 3/6 (50%) | 3/7 (42.9%) | 0/1 (0%) | 5/6 (83.3%) | 4/9 (44.4%) | 2/2 (100%) | 2/2 (100%) | 1/2 (50%) | 1/2 (50%) | 1/1 (100%) | |||||||||||||||||||||||||||
Serious Adverse Events |
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| Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine | ||||||||||||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/4 (75%) | 4/4 (100%) | 2/4 (50%) | 3/4 (75%) | 3/4 (75%) | 3/7 (42.9%) | 6/8 (75%) | 7/12 (58.3%) | 4/8 (50%) | 5/8 (62.5%) | 2/4 (50%) | 6/10 (60%) | 6/7 (85.7%) | 5/8 (62.5%) | 2/6 (33.3%) | 11/18 (61.1%) | 7/12 (58.3%) | 4/6 (66.7%) | 4/7 (57.1%) | 1/1 (100%) | 6/6 (100%) | 5/9 (55.6%) | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) | 1/2 (50%) | 1/1 (100%) | |||||||||||||||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Anaemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Febrile neutropenia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Neutropenia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cardiac arrest | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Cardiac tamponade | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Myocardial infarction | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pericardial effusion | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Supraventricular tachycardia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Endocrine disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adrenal insufficiency | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abdominal pain | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 2/12 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Constipation | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Diarrhoea | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Duodenitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Gastrointestinal haemorrhage | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Haematemesis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Ileus | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Intestinal obstruction | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Intestinal perforation | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Large intestinal haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Malignant gastrointestinal obstruction | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Melaena | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Nausea | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pancreatitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Rectal haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Small intestinal obstruction | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Upper gastrointestinal haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| General disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fatigue | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pyrexia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 2/18 (11.1%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholangitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hepatic failure | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Encephalitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Enterocolitis infectious | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Escherichia bacteraemia | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Infected fistula | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Lower respiratory tract infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pneumonia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 2/7 (28.6%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Sepsis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Septic shock | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Skin infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Soft tissue infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Urinary tract infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 2/18 (11.1%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Gastroenteritis radiation | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Infusion related reaction | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Procedural pain | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Investigations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alanine aminotransferase increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Aspartate aminotransferase increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood bilirubin increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood creatinine increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Platelet count decreased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cachexia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Decreased appetite | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dehydration | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypocalcaemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypoglycaemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hyponatraemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthralgia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Back pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pain in extremity | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Psoriatic arthropathy | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Malignant ascites | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Malignant neoplasm progression | 3/4 (75%) | 2/4 (50%) | 2/4 (50%) | 2/4 (50%) | 1/4 (25%) | 1/7 (14.3%) | 3/8 (37.5%) | 5/12 (41.7%) | 1/8 (12.5%) | 4/8 (50%) | 2/4 (50%) | 5/10 (50%) | 5/7 (71.4%) | 4/8 (50%) | 1/6 (16.7%) | 6/18 (33.3%) | 1/12 (8.3%) | 1/6 (16.7%) | 2/7 (28.6%) | 0/1 (0%) | 4/6 (66.7%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 1/1 (100%) | |||||||||||||||||||||||||||
| Metastases to spine | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pericarditis malignant | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bell's palsy | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Brain oedema | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Cerebrovascular accident | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hemiparesis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Secondary cerebellar degeneration | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Seizure | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Confusional state | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Delirium | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Acute kidney injury | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Haematuria | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hydronephrosis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dyspnoea | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 2/12 (16.7%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Haemoptysis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pleural effusion | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pneumonitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pneumothorax | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pulmonary embolism | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pulmonary haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Stridor | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Vascular disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypotension | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Escalation Part 1: BMS 20 mg Q2W | Escalation Part 1: BMS 40 mg Q2W | Escalation Part 1: BMS 80 mg Q2W | Escalation Part 1: BMS 160 mg Q2W | Escalation Part 1: BMS 320 mg Q2W | Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 40 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 80 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 160 mg + Nivo 240 mg Q2W | Escalation Part 2: BMS 320 mg + Nivo 240 mg Q2W | Escalation Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W | Escalation Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W | Expansion Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC) | Schedule and Dose Exploration Part 4: BMS 80 mg + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W | Safety Part 6A: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Expansion Part 6B: BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg Q3W / BMS 40 mg + Nivo 480 mg Q4W (RCC) | Safety Cohort Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Expansion Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W (NSCLC) | Schedule and Dose Exploration Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W | Schedule and Dose Exploration Part 8: Cohort 4- Nivo 480 mg Q4W | Exploration Part 9 Cohort 1: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine | ||||||||||||||||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 4/4 (100%) | 4/4 (100%) | 3/4 (75%) | 4/4 (100%) | 7/7 (100%) | 8/8 (100%) | 12/12 (100%) | 6/8 (75%) | 8/8 (100%) | 4/4 (100%) | 10/10 (100%) | 7/7 (100%) | 8/8 (100%) | 6/6 (100%) | 18/18 (100%) | 11/12 (91.7%) | 6/6 (100%) | 5/7 (71.4%) | 1/1 (100%) | 6/6 (100%) | 9/9 (100%) | 2/2 (100%) | 2/2 (100%) | 2/2 (100%) | 2/2 (100%) | 1/1 (100%) | |||||||||||||||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Anaemia | 0/4 (0%) | 1/4 (25%) | 2/4 (50%) | 0/4 (0%) | 0/4 (0%) | 3/7 (42.9%) | 4/8 (50%) | 2/12 (16.7%) | 1/8 (12.5%) | 1/8 (12.5%) | 0/4 (0%) | 3/10 (30%) | 2/7 (28.6%) | 3/8 (37.5%) | 2/6 (33.3%) | 8/18 (44.4%) | 5/12 (41.7%) | 2/6 (33.3%) | 2/7 (28.6%) | 0/1 (0%) | 1/6 (16.7%) | 3/9 (33.3%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 2/2 (100%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Lymph node pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Lymphadenopathy | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Neutropenia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Thrombocytopenia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arrhythmia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Atrial fibrillation | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Cardiac failure | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Palpitations | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Sinus tachycardia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Supraventricular tachycardia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Tachycardia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 1/7 (14.3%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ear pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Tinnitus | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Vertigo | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Endocrine disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adrenal insufficiency | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypothyroidism | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 2/8 (25%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Thyroiditis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Eye disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Blepharospasm | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Cataract | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Conjunctivitis allergic | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dry eye | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Eye irritation | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Eye pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Eyelid rash | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Lacrimation increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Macular degeneration | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Ocular hyperaemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Periorbital oedema | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Vision blurred | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Vitreous floaters | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abdominal discomfort | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Abdominal distension | 2/4 (50%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/1 (100%) | |||||||||||||||||||||||||||
| Abdominal pain | 1/4 (25%) | 1/4 (25%) | 0/4 (0%) | 2/4 (50%) | 0/4 (0%) | 1/7 (14.3%) | 2/8 (25%) | 2/12 (16.7%) | 2/8 (25%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 1/7 (14.3%) | 1/8 (12.5%) | 1/6 (16.7%) | 3/18 (16.7%) | 2/12 (16.7%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 2/9 (22.2%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Abdominal pain lower | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Abdominal pain upper | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Anal haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Anorectal discomfort | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Aphthous ulcer | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Ascites | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/1 (100%) | |||||||||||||||||||||||||||
| Constipation | 1/4 (25%) | 1/4 (25%) | 2/4 (50%) | 1/4 (25%) | 0/4 (0%) | 1/7 (14.3%) | 2/8 (25%) | 4/12 (33.3%) | 3/8 (37.5%) | 1/8 (12.5%) | 1/4 (25%) | 5/10 (50%) | 0/7 (0%) | 0/8 (0%) | 3/6 (50%) | 3/18 (16.7%) | 2/12 (16.7%) | 2/6 (33.3%) | 0/7 (0%) | 0/1 (0%) | 2/6 (33.3%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Diarrhoea | 0/4 (0%) | 1/4 (25%) | 1/4 (25%) | 1/4 (25%) | 1/4 (25%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 2/8 (25%) | 0/8 (0%) | 0/4 (0%) | 2/10 (20%) | 1/7 (14.3%) | 2/8 (25%) | 2/6 (33.3%) | 4/18 (22.2%) | 2/12 (16.7%) | 1/6 (16.7%) | 3/7 (42.9%) | 1/1 (100%) | 1/6 (16.7%) | 2/9 (22.2%) | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Diverticulum | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dry mouth | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 1/2 (50%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dyspepsia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dysphagia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Flatulence | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Gastrooesophageal reflux disease | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 2/12 (16.7%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Glossodynia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Haemorrhoids | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Large intestinal haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Mouth haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Nausea | 3/4 (75%) | 0/4 (0%) | 1/4 (25%) | 1/4 (25%) | 1/4 (25%) | 2/7 (28.6%) | 1/8 (12.5%) | 3/12 (25%) | 2/8 (25%) | 2/8 (25%) | 1/4 (25%) | 2/10 (20%) | 2/7 (28.6%) | 2/8 (25%) | 0/6 (0%) | 0/18 (0%) | 3/12 (25%) | 4/6 (66.7%) | 1/7 (14.3%) | 1/1 (100%) | 0/6 (0%) | 1/9 (11.1%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Odynophagia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Oral pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Rectal haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Retching | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Small intestinal obstruction | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Stomatitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Swollen tongue | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Vomiting | 2/4 (50%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 2/12 (16.7%) | 1/8 (12.5%) | 2/8 (25%) | 1/4 (25%) | 2/10 (20%) | 1/7 (14.3%) | 1/8 (12.5%) | 1/6 (16.7%) | 0/18 (0%) | 2/12 (16.7%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/1 (0%) | 1/6 (16.7%) | 1/9 (11.1%) | 1/2 (50%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| General disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Asthenia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 2/8 (25%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 2/6 (33.3%) | 3/9 (33.3%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Axillary pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Chest discomfort | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Chest pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Chills | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 2/7 (28.6%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 1/12 (8.3%) | 3/6 (50%) | 1/7 (14.3%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 1/1 (100%) | |||||||||||||||||||||||||||
| Early satiety | 1/4 (25%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Fatigue | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 1/7 (14.3%) | 1/8 (12.5%) | 2/12 (16.7%) | 5/8 (62.5%) | 4/8 (50%) | 0/4 (0%) | 2/10 (20%) | 1/7 (14.3%) | 2/8 (25%) | 2/6 (33.3%) | 7/18 (38.9%) | 3/12 (25%) | 4/6 (66.7%) | 3/7 (42.9%) | 1/1 (100%) | 1/6 (16.7%) | 4/9 (44.4%) | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Feeling cold | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Gait disturbance | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 2/8 (25%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Influenza like illness | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Injury associated with device | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Localised oedema | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Malaise | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Mass | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Mucosal inflammation | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Nodule | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Non-cardiac chest pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Oedema peripheral | 1/4 (25%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 2/12 (16.7%) | 0/8 (0%) | 1/8 (12.5%) | 1/4 (25%) | 0/10 (0%) | 1/7 (14.3%) | 2/8 (25%) | 0/6 (0%) | 4/18 (22.2%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/7 (0%) | 1/8 (12.5%) | 1/12 (8.3%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pyrexia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 1/4 (25%) | 2/7 (28.6%) | 2/8 (25%) | 5/12 (41.7%) | 0/8 (0%) | 2/8 (25%) | 1/4 (25%) | 4/10 (40%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 4/18 (22.2%) | 3/12 (25%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 1/2 (50%) | 1/2 (50%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Swelling face | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Temperature regulation disorder | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biliary obstruction | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Cholelithiasis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hyperbilirubinaemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Immune system disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Allergy to arthropod sting | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Seasonal allergy | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abdominal infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Bronchitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Candida infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Cellulitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Cryptosporidiosis infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Cystitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Ear infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Erysipelas | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Escherichia sepsis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Fungal infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Gastroenteritis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Gingivitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Nail infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Nasopharyngitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 2/8 (25%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Oral candidiasis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Oral herpes | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Peritonitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pharyngitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pharyngitis streptococcal | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pneumonia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 2/12 (16.7%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Rash pustular | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Respiratory tract infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 2/9 (22.2%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Sepsis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Sinusitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Skin infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Sputum purulent | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Upper respiratory tract infection | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Urinary tract infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/7 (0%) | 2/8 (25%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 2/18 (11.1%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Viral upper respiratory tract infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Wound infection | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ankle fracture | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Contusion | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Fall | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Infusion related reaction | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 3/8 (37.5%) | 2/6 (33.3%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 2/6 (33.3%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Muscle strain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Post procedural haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Procedural pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Thermal burn | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Vascular access complication | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Vascular access site occlusion | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Investigations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alanine aminotransferase increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 1/7 (14.3%) | 2/8 (25%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 2/4 (50%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Ammonia increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Amylase increased | 1/4 (25%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 3/18 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Aspartate aminotransferase increased | 0/4 (0%) | 2/4 (50%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 1/7 (14.3%) | 2/8 (25%) | 1/12 (8.3%) | 1/8 (12.5%) | 0/8 (0%) | 2/4 (50%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood alkaline phosphatase increased | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 1/4 (25%) | 0/4 (0%) | 3/7 (42.9%) | 2/8 (25%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 2/7 (28.6%) | 1/8 (12.5%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood bilirubin increased | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 3/8 (37.5%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood chloride decreased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood chloride increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood creatine phosphokinase increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood creatinine increased | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 2/12 (16.7%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 1/6 (16.7%) | 5/18 (27.8%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood glucose increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood lactate dehydrogenase increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood lactic acid increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood phosphorus decreased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood thyroid stimulating hormone decreased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood thyroid stimulating hormone increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Blood urea increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Carbon dioxide decreased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Creatinine renal clearance decreased | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Electrocardiogram QT prolonged | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Gamma-glutamyltransferase increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 2/18 (11.1%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Glomerular filtration rate decreased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Lipase increased | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 3/18 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Lymph node palpable | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Lymphocyte count decreased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Neutrophil count decreased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Neutrophil count increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Platelet count decreased | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 2/7 (28.6%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Platelet count increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Serum ferritin decreased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Urine output decreased | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Urine protein/creatinine ratio increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Weight decreased | 1/4 (25%) | 2/4 (50%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 2/12 (16.7%) | 1/8 (12.5%) | 0/8 (0%) | 1/4 (25%) | 2/10 (20%) | 0/7 (0%) | 2/8 (25%) | 2/6 (33.3%) | 2/18 (11.1%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 1/1 (100%) | 1/6 (16.7%) | 1/9 (11.1%) | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Weight increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| White blood cell count decreased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| White blood cell count increased | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Decreased appetite | 1/4 (25%) | 0/4 (0%) | 1/4 (25%) | 1/4 (25%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 1/12 (8.3%) | 2/8 (25%) | 7/8 (87.5%) | 1/4 (25%) | 2/10 (20%) | 0/7 (0%) | 3/8 (37.5%) | 2/6 (33.3%) | 3/18 (16.7%) | 1/12 (8.3%) | 3/6 (50%) | 0/7 (0%) | 1/1 (100%) | 3/6 (50%) | 2/9 (22.2%) | 1/2 (50%) | 1/2 (50%) | 1/2 (50%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dehydration | 1/4 (25%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 1/1 (100%) | 2/6 (33.3%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Diabetes mellitus | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Gout | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypercalcaemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 2/12 (16.7%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hyperglycaemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 1/18 (5.6%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hyperkalaemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 2/8 (25%) | 1/12 (8.3%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypernatraemia | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hyperuricaemia | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypoalbuminaemia | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 2/8 (25%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 2/7 (28.6%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypocalcaemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypoglycaemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 2/12 (16.7%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypokalaemia | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 2/8 (25%) | 0/6 (0%) | 1/18 (5.6%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypomagnesaemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 2/6 (33.3%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hyponatraemia | 1/4 (25%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypophosphataemia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Type 2 diabetes mellitus | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthralgia | 0/4 (0%) | 1/4 (25%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 1/12 (8.3%) | 2/8 (25%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 1/6 (16.7%) | 2/18 (11.1%) | 2/12 (16.7%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 3/9 (33.3%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Arthritis | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Back pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 1/7 (14.3%) | 0/8 (0%) | 1/12 (8.3%) | 1/8 (12.5%) | 2/8 (25%) | 1/4 (25%) | 1/10 (10%) | 0/7 (0%) | 1/8 (12.5%) | 2/6 (33.3%) | 3/18 (16.7%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Bone pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Bursitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Flank pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Joint range of motion decreased | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Joint stiffness | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Muscle spasms | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 3/8 (37.5%) | 1/4 (25%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Muscle twitching | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Muscular weakness | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Musculoskeletal chest pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 2/9 (22.2%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Musculoskeletal discomfort | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Musculoskeletal pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Myalgia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/1 (100%) | |||||||||||||||||||||||||||
| Neck pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pain in extremity | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 1/8 (12.5%) | 1/8 (12.5%) | 1/4 (25%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 3/18 (16.7%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 1/9 (11.1%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Psoriatic arthropathy | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Rotator cuff syndrome | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Spinal pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Weight bearing difficulty | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lymphangiosis carcinomatosa | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Malignant neoplasm progression | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Metastases to central nervous system | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Tumour pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aphasia | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Balance disorder | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Bell's palsy | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Disturbance in attention | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dizziness | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 3/8 (37.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 2/18 (11.1%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dysgeusia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 1/1 (100%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Head discomfort | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Headache | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/8 (0%) | 2/8 (25%) | 0/4 (0%) | 1/10 (10%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypoaesthesia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Lethargy | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Memory impairment | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Migraine | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Neuralgia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Neuropathy peripheral | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 1/6 (16.7%) | 1/18 (5.6%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Peripheral sensory neuropathy | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Presyncope | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Sciatica | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Secondary cerebellar degeneration | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Taste disorder | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Tremor | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Affect lability | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Anxiety | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/1 (0%) | 0/6 (0%) | 2/9 (22.2%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Bradyphrenia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Confusional state | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 2/12 (16.7%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Depression | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Insomnia | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 2/6 (33.3%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Acute kidney injury | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dysuria | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Haematuria | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 2/18 (11.1%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Micturition urgency | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Nephritis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pollakiuria | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Proteinuria | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Renal disorder | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 2/18 (11.1%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Renal failure | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Urinary incontinence | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Urinary retention | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Breast pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pelvic pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Scrotal oedema | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Scrotal pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Vaginal discharge | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bronchospasm | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Cough | 1/4 (25%) | 1/4 (25%) | 1/4 (25%) | 1/4 (25%) | 2/4 (50%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 1/8 (12.5%) | 2/8 (25%) | 1/4 (25%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 2/6 (33.3%) | 2/18 (11.1%) | 0/12 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 1/1 (100%) | 1/6 (16.7%) | 4/9 (44.4%) | 1/2 (50%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dysphonia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dyspnoea | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 1/7 (14.3%) | 0/8 (0%) | 2/12 (16.7%) | 2/8 (25%) | 1/8 (12.5%) | 0/4 (0%) | 2/10 (20%) | 2/7 (28.6%) | 0/8 (0%) | 1/6 (16.7%) | 1/18 (5.6%) | 4/12 (33.3%) | 2/6 (33.3%) | 2/7 (28.6%) | 1/1 (100%) | 1/6 (16.7%) | 5/9 (55.6%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dyspnoea exertional | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Epistaxis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Haemoptysis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 3/9 (33.3%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hiccups | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypoxia | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Nasal congestion | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Oropharyngeal pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pleural effusion | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pleuritic pain | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pneumothorax | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Productive cough | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 1/8 (12.5%) | 0/4 (0%) | 1/10 (10%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pulmonary embolism | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pulmonary haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Respiratory tract congestion | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Rhinitis allergic | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Sinus congestion | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Wheezing | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 2/7 (28.6%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alopecia | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Autoimmune dermatitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Dry skin | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Eczema | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Erythema | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hyperhidrosis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hyperkeratosis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Nail disorder | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Pruritus | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 2/7 (28.6%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 1/4 (25%) | 3/10 (30%) | 1/7 (14.3%) | 1/8 (12.5%) | 2/6 (33.3%) | 2/18 (11.1%) | 3/12 (25%) | 3/6 (50%) | 1/7 (14.3%) | 0/1 (0%) | 1/6 (16.7%) | 5/9 (55.6%) | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) | 1/2 (50%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Psoriasis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Rash | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 2/10 (20%) | 1/7 (14.3%) | 1/8 (12.5%) | 0/6 (0%) | 1/18 (5.6%) | 0/12 (0%) | 2/6 (33.3%) | 1/7 (14.3%) | 0/1 (0%) | 1/6 (16.7%) | 2/9 (22.2%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Rash erythematous | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Rash maculo-papular | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 1/4 (25%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 1/12 (8.3%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 1/9 (11.1%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Rash papular | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Rash pruritic | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Skin disorder | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Skin haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Skin ulcer | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Vascular disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Deep vein thrombosis | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Embolism | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Embolism venous | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 1/12 (8.3%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Haemorrhage | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 1/10 (10%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hot flush | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypertension | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 1/12 (8.3%) | 0/8 (0%) | 1/8 (12.5%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 0/6 (0%) | 2/18 (11.1%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Hypotension | 0/4 (0%) | 1/4 (25%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 0/8 (0%) | 1/6 (16.7%) | 0/18 (0%) | 0/12 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/1 (0%) | 1/6 (16.7%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Phlebitis | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
| Thrombophlebitis superficial | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) | 0/7 (0%) | 0/8 (0%) | 0/12 (0%) | 0/8 (0%) | 0/8 (0%) | 0/4 (0%) | 0/10 (0%) | 0/7 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/18 (0%) | 0/12 (0%) | 0/6 (0%) | 0/7 (0%) | 0/1 (0%) | 0/6 (0%) | 0/9 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/1 (0%) | |||||||||||||||||||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
| Name/Title | Bristol-Myers Squibb Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | Please email |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT02737475
Other Study ID Numbers:
- CA012-004
- 2015-004816-39
First Posted:
Apr 14, 2016
Last Update Posted:
Jan 25, 2022
Last Verified:
Dec 1, 2021