Nivolumab (BMS-936558; MDX-1106) in Combination With Sunitinib, Pazopanib, or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma (RCC) (CheckMate 016)
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT01472081
Collaborator
Ono Pharmaceutical Co. Ltd (Industry)
194
14
5
111.8
13.9
0.1
Study Details
Study Description
Brief Summary
The purpose is to determine the safety, effectiveness and best dose to use when giving Nivolumab in combination with Sunitinib, Pazopanib, or Ipilimumab for the treatment of metastatic renal cell carcinoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
194 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study of Nivolumab (BMS-936558) Plus Sunitinib, Pazopanib or Ipilimumab in Subjects With Metastatic Renal Cell Carcinoma
Actual Study Start Date
:
Feb 9, 2012
Actual Primary Completion Date
:
Feb 2, 2016
Actual Study Completion Date
:
Jun 3, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm S: Nivolumab + Sunitinib Nivolumab 0.3, 2.0 (starting dose), 5.0 mg/kg solution intravenously every 21 days until Progressive disease (PD), toxicity or discontinue for other reasons Sunitinib 50 mg capsule by mouth on Days 1-28 of 42 day cycle until Progressive disease (PD), toxicity or discontinue for other reasons |
Biological: Nivolumab
Other Names:
Drug: Sunitinib
Other Names:
|
| Experimental: Arm P: Nivolumab + Pazopanib Nivolumab 0.3, 2.0 (starting dose), 5.0 mg/kg solution intravenously every 21 days until Progressive disease (PD), toxicity or discontinue for other reasons Pazopanib 800 mg tablet by mouth daily until Progressive disease (PD), toxicity or discontinue for other reasons |
Biological: Nivolumab
Other Names:
Biological: Pazopanib
Other Names:
|
| Experimental: Arm I-1: Nivolumab + Ipilimumab Nivolumab 3 mg/kg solution intravenously (IV) every 21 days during Induction phase and every 14 days during Maintenance phase until Progressive disease (PD), toxicity or discontinue for other reasons Ipilimumab 1mg/kg solution intravenously (IV) every 21 days during Induction phase (Ipilimumab will not be administered during Maintenance phase) until Progressive disease (PD), toxicity or discontinue for other reasons |
Biological: Nivolumab
Other Names:
Biological: Ipilimumab
Other Names:
|
| Experimental: Arm I-3: Nivolumab + Ipilimumab Nivolumab 1mg/kg solution intravenously (IV) every 21 days during Induction phase and 3mg/kg solution intravenously (IV) every 14 days during Maintenance phase Ipilimumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase. Ipilimumab will not be administered during Maintenance phase |
Biological: Nivolumab
Other Names:
Biological: Ipilimumab
Other Names:
|
| Experimental: Arm IN-3: Nivolumab+Ipilimumab Nivolumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase and 3mg/kg solution intravenously (IV) every 14 days during Maintenance phase Ipilimumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase. Ipilimumab will not be administered during Maintenance phase |
Biological: Nivolumab
Other Names:
Biological: Ipilimumab
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation [From date of first dose to date of last dose plus 100 days (assessed up to March 2016, approximately 49 months)]
Safety assessments by treatment arm and dose level were based on incidence of AEs, and the incidence of serious adverse events (SAEs). AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling.
Secondary Outcome Measures
- Best Overall Response Rate (BOR) [From date of first dose to date of disease progression or subsequent anti-cancer therapy, whichever occurred first (assessed up to March 2016, approximately 49 months)]
BOR was defined as the best response designation over the study as a whole, recorded between the date of first dose of study medication and the date of objectively documented progression per RECIST 1.1 criteria or the date of subsequent anti-cancer therapy, whichever occurred first. CR = Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD = At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
- Objective Response Rate (ORR) [From date of first dose to interim analysis (Assessed up to March 2016, approximately 49 months)]
ORR was defined as the proportion of participants who achieved a BOR of either complete response (CR) or partial response (PR) in the population of interest. CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- Duration of Response (DOR) [From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)]
DOR was computed for participants with BOR of CR or PR only, and defined as the time between the date of first documented objective response and the date of the first subsequent disease progression or death. Participants who remained alive and had not progressed were censored on the last tumor assessment date (prior to subsequent cancer therapy).
- Rate of Progression-free Survival (PFS) at Week 24 [24 weeks]
Rate of PFS at week 24 was defined as the proportion of participants remaining progression free or surviving at 24 weeks, calculated by the product-limit method (Kaplan-Meier estimate) which took into account censored data. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication.
- Progression-free Survival (PFS) [From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)]
PFS was defined as the time from the date of first dose of study medication to the date of first disease progression or death. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria:
-
Subjects with histological confirmation of RCC
-
Advanced or metastatic disease
-
Measurable disease as defined by RECIST 1.1 criteria
-
Karnofsky Performance Status (KPS) ≥80%
-
Available tumor tissue (archival or recent acquisition)
-
Subjects enrolled in the I-1, I-3 expansion arms and IN-3 addition arms must not have received any prior systemic therapy for RCC with the following exceptions:
-
One prior adjuvant or neoadjuvant therapy for localized or locally advanced RCC is allowed provided recurrence occurred ≥ 6 months after the last dose of the adjuvant or neoadjuvant therapy
-
Only prior cytokine based treatment for metastatic RCC [eg, interferon-alpha (IFN-alpha) or interleukin 2 (IL-2)] as prior therapy is allowed
Exclusion Criteria:
-
Active central nervous system (CNS) metastases
-
Active or history of autoimmune disease
-
Ongoing symptomatic cardiac dysrhythmias or uncontrolled atrial fibrillation
-
History of cerebrovascular accident including transient ischemic attack within the past 12 months
-
History of pulmonary embolism or deep vein thrombosis (DVT) within the past 6 months
-
Chronic systemic steroids (>10 mg/day Prednisone equivalents) or any other immunosuppressive agents
-
White blood cell (WBC) <2,000/mm3
-
Neutrophiles <1,500/mm3
-
Platelets <100,000/mm3
-
Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >3x upper limit of normal (ULN)
-
Total Bilirubin >1.5x ULN (except subjects with Gilbert syndrome, total bilirubin <3.0 mg/dL)
-
Cardiac ejection fraction <LLN (lower limit of normal)
-
Serum creatinine >1.5x ULN or creatinine clearance <40 mL/min (Cockroft-Gault formula)
Exclusion Criteria for Arm S and Arm P only:
-
For dose escalation cohorts - subjects who received prior Sunitinib or Pazopanib and required permanent discontinuation due to toxicity or required dose reduction or delay during the first 12 weeks of therapy due to toxicity, or received both prior Sunitinib and Pazopanib
-
Poorly controlled hypertension
-
Active bleeding or bleeding susceptibility
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City Of Hope | Duarte | California | United States | 91010-3000 |
| 2 | Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins | Baltimore | Maryland | United States | 21287 |
| 3 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 4 | Dartmouth-Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 5 | Memorial Sloan Kettering Nassau | New York | New York | United States | 10065 |
| 6 | Blumenthal Cancer Center | Charlotte | North Carolina | United States | 28204 |
| 7 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 8 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
| 9 | Tennessee Oncology, PLLC | Nashville | Tennessee | United States | 37203 |
| 10 | University Of Texas M.D. Anderson Cancer Center | Houston | Texas | United States | 77030-4009 |
| 11 | Tom Baker Cancer Centre | Calgary | Alberta | Canada | T2N 4N2 |
| 12 | Cross Cancer Institute | Edmonton | Alberta | Canada | T6G 1Z2 |
| 13 | BC Cancer Agency - Vancouver Centre | Vancouver | British Columbia | Canada | V5Z 4E6 |
| 14 | Princess Margaret Cancer Centre | Toronto | Ontario | Canada | M5G 1Z5 |
Sponsors and Collaborators
- Bristol-Myers Squibb
- Ono Pharmaceutical Co. Ltd
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- BMS Clinical Trial Information
- BMS Clinical Trial Patient Recruiting
- Investigator Inquiry Form
- FDA Safety Alerts and Recalls
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01472081
Other Study ID Numbers:
- CA209-016
First Posted:
Nov 16, 2011
Last Update Posted:
Dec 2, 2021
Last Verified:
Nov 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 | 194 participants were enrolled; 153 were treated. Participants were enrolled but not treated due to the following reasons: withdrawal of consent (n=5), no longer met study criteria (n=32), administrative reason by sponsor (n=1), or other reasons (n=3) |
| Arm/Group Title | Arm S: SUN + NIV2 | Arm S: SUN + NIV5 | Arm P: PAZ + NIV2 | Arm I-1: IPI1 + NIV3 | Arm I-3: IPI3 + NIV1 | Arm IN-3: IPI3 + NIV3 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. |
| Period Title: Overall Study | ||||||
| STARTED | 7 | 26 | 20 | 47 | 47 | 6 |
| COMPLETED | 0 | 0 | 0 | 1 | 0 | 0 |
| NOT COMPLETED | 7 | 26 | 20 | 46 | 47 | 6 |
Baseline Characteristics
| Arm/Group Title | Arm S: SUN + NIV2 | Arm S: SUN + NIV5 | Arm P: PAZ + NIV2 | Arm I-1: IPI1 + NIV3 | Arm I-3: IPI3 + NIV1 | Arm IN-3: IPI3 + NIV3 | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Total of all reporting groups |
| Overall Participants | 7 | 26 | 20 | 47 | 47 | 6 | 153 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
56.9
(11.36)
|
58.3
(8.62)
|
56.3
(8.52)
|
53.0
(8.97)
|
55.6
(11.58)
|
54.8
(2.71)
|
55.4
(9.71)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
0
0%
|
7
26.9%
|
2
10%
|
14
29.8%
|
9
19.1%
|
1
16.7%
|
33
21.6%
|
| Male |
7
100%
|
19
73.1%
|
18
90%
|
33
70.2%
|
38
80.9%
|
5
83.3%
|
120
78.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||
| Hispanic or Latino |
0
0%
|
2
7.7%
|
0
0%
|
1
2.1%
|
2
4.3%
|
1
16.7%
|
6
3.9%
|
| Not Hispanic or Latino |
7
100%
|
22
84.6%
|
18
90%
|
42
89.4%
|
40
85.1%
|
5
83.3%
|
134
87.6%
|
| Unknown or Not Reported |
0
0%
|
2
7.7%
|
2
10%
|
4
8.5%
|
5
10.6%
|
0
0%
|
13
8.5%
|
| Race (NIH/OMB) (Count of Participants) | |||||||
| American Indian or Alaska Native |
0
0%
|
1
3.8%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.7%
|
| Asian |
0
0%
|
1
3.8%
|
0
0%
|
2
4.3%
|
0
0%
|
0
0%
|
3
2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
14.3%
|
1
3.8%
|
1
5%
|
1
2.1%
|
1
2.1%
|
0
0%
|
5
3.3%
|
| White |
6
85.7%
|
22
84.6%
|
18
90%
|
44
93.6%
|
45
95.7%
|
6
100%
|
141
92.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
1
3.8%
|
1
5%
|
0
0%
|
1
2.1%
|
0
0%
|
3
2%
|
Outcome Measures
| Title | Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation |
|---|---|
| Description | Safety assessments by treatment arm and dose level were based on incidence of AEs, and the incidence of serious adverse events (SAEs). AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. |
| Time Frame | From date of first dose to date of last dose plus 100 days (assessed up to March 2016, approximately 49 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Arm S: SUN + NIV2 | Arm S: SUN + NIV5 | Arm P: PAZ + NIV2 | Arm I-1: IPI1 + NIV3 | Arm I-3: IPI3 + NIV1 | Arm IN-3: IPI3 + NIV3 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. |
| Measure Participants | 7 | 26 | 20 | 47 | 47 | 6 |
| All-causality SAEs (any grade) |
3
42.9%
|
16
61.5%
|
13
65%
|
29
61.7%
|
30
63.8%
|
4
66.7%
|
| All-causality SAEs (grade 3-4) |
1
14.3%
|
14
53.8%
|
10
50%
|
20
42.6%
|
24
51.1%
|
4
66.7%
|
| Drug-related SAEs (any grade) |
2
28.6%
|
12
46.2%
|
2
10%
|
11
23.4%
|
16
34%
|
3
50%
|
| Drug-related SAEs (grade 3-4) |
0
0%
|
10
38.5%
|
2
10%
|
9
19.1%
|
16
34%
|
3
50%
|
| All-cause AEs led to discontinuation (any grade) |
3
42.9%
|
10
38.5%
|
5
25%
|
5
10.6%
|
15
31.9%
|
2
33.3%
|
| All-cause AEs led to discontinuation (grade 3-4) |
2
28.6%
|
9
34.6%
|
4
20%
|
3
6.4%
|
11
23.4%
|
0
0%
|
| All-Causality AEs (any grade) |
7
100%
|
26
100%
|
20
100%
|
47
100%
|
47
100%
|
6
100%
|
| All-Causality AEs (grade 3-4) |
6
85.7%
|
24
92.3%
|
16
80%
|
33
70.2%
|
34
72.3%
|
6
100%
|
| Drug-related AEs (any grade) |
7
100%
|
26
100%
|
20
100%
|
43
91.5%
|
45
95.7%
|
6
100%
|
| Drug-related AEs (grade 3-4) |
5
71.4%
|
22
84.6%
|
14
70%
|
18
38.3%
|
29
61.7%
|
5
83.3%
|
| Title | Best Overall Response Rate (BOR) |
|---|---|
| Description | BOR was defined as the best response designation over the study as a whole, recorded between the date of first dose of study medication and the date of objectively documented progression per RECIST 1.1 criteria or the date of subsequent anti-cancer therapy, whichever occurred first. CR = Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD = At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Time Frame | From date of first dose to date of disease progression or subsequent anti-cancer therapy, whichever occurred first (assessed up to March 2016, approximately 49 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Arm S: SUN + NIV2 | Arm S: SUN + NIV5 | Arm P: PAZ + NIV2 | Arm I-1: IPI1 + NIV3 | Arm I-3: IPI3 + NIV1 | Arm IN-3: IPI3 + NIV3 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. |
| Measure Participants | 7 | 26 | 20 | 47 | 47 | 6 |
| Complete Response |
1
14.3%
|
0
0%
|
1
5%
|
5
10.6%
|
0
0%
|
0
0%
|
| Partial Response |
5
71.4%
|
11
42.3%
|
8
40%
|
14
29.8%
|
19
40.4%
|
0
0%
|
| Stable Disease |
1
14.3%
|
11
42.3%
|
7
35%
|
19
40.4%
|
17
36.2%
|
5
83.3%
|
| Progressive Disease |
0
0%
|
1
3.8%
|
4
20%
|
8
17%
|
8
17%
|
1
16.7%
|
| Unable to Determine |
0
0%
|
3
11.5%
|
0
0%
|
1
2.1%
|
3
6.4%
|
0
0%
|
| Title | Objective Response Rate (ORR) |
|---|---|
| Description | ORR was defined as the proportion of participants who achieved a BOR of either complete response (CR) or partial response (PR) in the population of interest. CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Time Frame | From date of first dose to interim analysis (Assessed up to March 2016, approximately 49 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Arm S: SUN + NIV2 | Arm S: SUN + NIV5 | Arm P: PAZ + NIV2 | Arm I-1: IPI1 + NIV3 | Arm I-3: IPI3 + NIV1 | Arm IN-3: IPI3 + NIV3 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. |
| Measure Participants | 7 | 26 | 20 | 47 | 47 | 6 |
| Number (95% Confidence Interval) [percentage of participants] |
85.7
1224.3%
|
42.3
162.7%
|
45.0
225%
|
40.4
86%
|
40.4
86%
|
0
0%
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | DOR was computed for participants with BOR of CR or PR only, and defined as the time between the date of first documented objective response and the date of the first subsequent disease progression or death. Participants who remained alive and had not progressed were censored on the last tumor assessment date (prior to subsequent cancer therapy). |
| Time Frame | From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Arm S: SUN + NIV2 | Arm S: SUN + NIV5 | Arm P: PAZ + NIV2 | Arm I-1: IPI1 + NIV3 | Arm I-3: IPI3 + NIV1 | Arm IN-3: IPI3 + NIV3 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. |
| Measure Participants | 7 | 26 | 20 | 47 | 47 | 6 |
| Median (95% Confidence Interval) [weeks] |
45.6
|
78.1
|
30.1
|
88.7
|
85.9
|
NA
|
| Title | Rate of Progression-free Survival (PFS) at Week 24 |
|---|---|
| Description | Rate of PFS at week 24 was defined as the proportion of participants remaining progression free or surviving at 24 weeks, calculated by the product-limit method (Kaplan-Meier estimate) which took into account censored data. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Arm S: SUN + NIV2 | Arm S: SUN + NIV5 | Arm P: PAZ + NIV2 | Arm I-1: IPI1 + NIV3 | Arm I-3: IPI3 + NIV1 | Arm IN-3: IPI3 + NIV3 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. |
| Measure Participants | 7 | 26 | 20 | 47 | 47 | 6 |
| Number (95% Confidence Interval) [Percentage of participants with PFS] |
100
1428.6%
|
72.9
280.4%
|
54.9
274.5%
|
55.6
118.3%
|
63.8
135.7%
|
NA
NaN
|
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from the date of first dose of study medication to the date of first disease progression or death. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication. |
| Time Frame | From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Arm S: SUN + NIV2 | Arm S: SUN + NIV5 | Arm P: PAZ + NIV2 | Arm I-1: IPI1 + NIV3 | Arm I-3: IPI3 + NIV1 | Arm IN-3: IPI3 + NIV3 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. |
| Measure Participants | 7 | 26 | 20 | 47 | 47 | 6 |
| Median (95% Confidence Interval) [months] |
11.3
|
12.7
|
7.2
|
7.7
|
9.4
|
8.5
|
Adverse Events
| Time Frame | From first dose to date of last dose plus 100 days | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | SUNITINIB+NIVOLUMAB | PAZOPANIB+NIVOLUMAB | NIVO 3+IPI 1 (MG/KG) | NIVO 1+IPI 3 (MG/KG) | NIVO 3+IPI 3 (MG/KG) | |||||
| Arm/Group Description | Nivolumab (2mg/kg or 5mg/kg)administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays. | |||||
All Cause Mortality |
||||||||||
| SUNITINIB+NIVOLUMAB | PAZOPANIB+NIVOLUMAB | NIVO 3+IPI 1 (MG/KG) | NIVO 1+IPI 3 (MG/KG) | NIVO 3+IPI 3 (MG/KG) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| SUNITINIB+NIVOLUMAB | PAZOPANIB+NIVOLUMAB | NIVO 3+IPI 1 (MG/KG) | NIVO 1+IPI 3 (MG/KG) | NIVO 3+IPI 3 (MG/KG) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/33 (57.6%) | 13/20 (65%) | 29/47 (61.7%) | 30/47 (63.8%) | 4/6 (66.7%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Methaemoglobinaemia | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Thrombocytopenia | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Lymphadenopathy | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Cardiac disorders | ||||||||||
| Myocardial ischaemia | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Sinus tachycardia | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Atrial fibrillation | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Endocrine disorders | ||||||||||
| Adrenal insufficiency | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Hyperthyroidism | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Hypophysitis | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Hypopituitarism | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Eye disorders | ||||||||||
| Diplopia | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/33 (0%) | 1/20 (5%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Autoimmune colitis | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Colitis | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 6/47 (12.8%) | 0/6 (0%) | |||||
| Diarrhoea | 2/33 (6.1%) | 2/20 (10%) | 4/47 (8.5%) | 6/47 (12.8%) | 1/6 (16.7%) | |||||
| Duodenitis | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Erosive duodenitis | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Gastritis erosive | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Large intestinal obstruction | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Nausea | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Small intestinal obstruction | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Vomiting | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Gastric haemorrhage | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Lower gastrointestinal haemorrhage | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Upper gastrointestinal haemorrhage | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| General disorders | ||||||||||
| Chills | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Hernia | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Mucosal ulceration | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Pain | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 4/47 (8.5%) | 0/6 (0%) | |||||
| Pyrexia | 1/33 (3%) | 2/20 (10%) | 4/47 (8.5%) | 3/47 (6.4%) | 2/6 (33.3%) | |||||
| Sudden death | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Systemic inflammatory response syndrome | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Hepatobiliary disorders | ||||||||||
| Autoimmune hepatitis | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Cholangitis | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Drug-induced liver injury | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Hepatitis acute | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Infections and infestations | ||||||||||
| Appendicitis perforated | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Bacteraemia | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Enterocolitis infectious | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Gastroenteritis | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Gastroenteritis viral | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Lung infection | 0/33 (0%) | 0/20 (0%) | 2/47 (4.3%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Pneumonia | 1/33 (3%) | 2/20 (10%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Pneumonia legionella | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Skin infection | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Viral infection | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Localised infection | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Pneumocystis jirovecii pneumonia | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Ankle fracture | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Fracture | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Spinal fracture | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Investigations | ||||||||||
| Alanine aminotransferase increased | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 4/47 (8.5%) | 0/6 (0%) | |||||
| Aspartate aminotransferase increased | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 4/47 (8.5%) | 0/6 (0%) | |||||
| Blood bilirubin increased | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Blood creatinine increased | 0/33 (0%) | 1/20 (5%) | 2/47 (4.3%) | 0/47 (0%) | 0/6 (0%) | |||||
| Lipase increased | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Platelet count decreased | 1/33 (3%) | 0/20 (0%) | 2/47 (4.3%) | 0/47 (0%) | 0/6 (0%) | |||||
| Transaminases increased | 1/33 (3%) | 0/20 (0%) | 1/47 (2.1%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 2/33 (6.1%) | 2/20 (10%) | 0/47 (0%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Diabetic ketoacidosis | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Hypercalcaemia | 0/33 (0%) | 0/20 (0%) | 2/47 (4.3%) | 0/47 (0%) | 0/6 (0%) | |||||
| Hyponatraemia | 3/33 (9.1%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Hyperkalaemia | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Back pain | 0/33 (0%) | 0/20 (0%) | 2/47 (4.3%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Muscular weakness | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Musculoskeletal pain | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Neck pain | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Musculoskeletal chest pain | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Pain in extremity | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Malignant ascites | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Malignant neoplasm progression | 1/33 (3%) | 2/20 (10%) | 6/47 (12.8%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Metastases to bone | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Tumour flare | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Metastases to central nervous system | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Nervous system disorders | ||||||||||
| Balance disorder | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Headache | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Neuropathy peripheral | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Peripheral motor neuropathy | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Seizure | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Spinal cord compression | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Syncope | 1/33 (3%) | 1/20 (5%) | 0/47 (0%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Transient global amnesia | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Transient ischaemic attack | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Haemorrhage intracranial | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Posterior reversible encephalopathy syndrome | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Acute kidney injury | 3/33 (9.1%) | 0/20 (0%) | 3/47 (6.4%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Renal failure | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Atelectasis | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Cough | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Dyspnoea | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 4/47 (8.5%) | 0/6 (0%) | |||||
| Haemoptysis | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Hypoxia | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Pleural effusion | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Pneumonitis | 1/33 (3%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Pulmonary embolism | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Rash maculo-papular | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Vascular disorders | ||||||||||
| Haemorrhage | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Hypertension | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Hypotension | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Orthostatic hypotension | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Thrombosis | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| SUNITINIB+NIVOLUMAB | PAZOPANIB+NIVOLUMAB | NIVO 3+IPI 1 (MG/KG) | NIVO 1+IPI 3 (MG/KG) | NIVO 3+IPI 3 (MG/KG) | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 33/33 (100%) | 20/20 (100%) | 47/47 (100%) | 46/47 (97.9%) | 6/6 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 8/33 (24.2%) | 3/20 (15%) | 7/47 (14.9%) | 10/47 (21.3%) | 1/6 (16.7%) | |||||
| Leukopenia | 3/33 (9.1%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Neutropenia | 5/33 (15.2%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Thrombocytopenia | 4/33 (12.1%) | 0/20 (0%) | 2/47 (4.3%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 0/33 (0%) | 1/20 (5%) | 1/47 (2.1%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Bradycardia | 0/33 (0%) | 0/20 (0%) | 2/47 (4.3%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Left ventricular dysfunction | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Palpitations | 1/33 (3%) | 1/20 (5%) | 6/47 (12.8%) | 3/47 (6.4%) | 1/6 (16.7%) | |||||
| Tachycardia | 1/33 (3%) | 0/20 (0%) | 5/47 (10.6%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Ear congestion | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Tinnitus | 1/33 (3%) | 2/20 (10%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Vertigo | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Endocrine disorders | ||||||||||
| Adrenal insufficiency | 0/33 (0%) | 0/20 (0%) | 2/47 (4.3%) | 6/47 (12.8%) | 2/6 (33.3%) | |||||
| Autoimmune thyroiditis | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Cushingoid | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Endocrine disorder | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Hyperthyroidism | 5/33 (15.2%) | 0/20 (0%) | 3/47 (6.4%) | 8/47 (17%) | 3/6 (50%) | |||||
| Hypothyroidism | 10/33 (30.3%) | 4/20 (20%) | 10/47 (21.3%) | 13/47 (27.7%) | 5/6 (83.3%) | |||||
| Lymphocytic hypophysitis | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Autoimmune hypothyroidism | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Eye disorders | ||||||||||
| Dry eye | 2/33 (6.1%) | 0/20 (0%) | 0/47 (0%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Eye pain | 0/33 (0%) | 1/20 (5%) | 1/47 (2.1%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Lacrimation increased | 4/33 (12.1%) | 0/20 (0%) | 3/47 (6.4%) | 5/47 (10.6%) | 1/6 (16.7%) | |||||
| Ocular hyperaemia | 1/33 (3%) | 0/20 (0%) | 1/47 (2.1%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Periorbital oedema | 5/33 (15.2%) | 0/20 (0%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Photopsia | 0/33 (0%) | 2/20 (10%) | 2/47 (4.3%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Vision blurred | 2/33 (6.1%) | 1/20 (5%) | 6/47 (12.8%) | 5/47 (10.6%) | 1/6 (16.7%) | |||||
| Visual impairment | 1/33 (3%) | 1/20 (5%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Vitreous detachment | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Vitreous floaters | 2/33 (6.1%) | 2/20 (10%) | 2/47 (4.3%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Vitreous haemorrhage | 1/33 (3%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal distension | 3/33 (9.1%) | 4/20 (20%) | 4/47 (8.5%) | 5/47 (10.6%) | 1/6 (16.7%) | |||||
| Abdominal pain | 5/33 (15.2%) | 7/20 (35%) | 10/47 (21.3%) | 12/47 (25.5%) | 2/6 (33.3%) | |||||
| Abdominal pain lower | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Abdominal pain upper | 3/33 (9.1%) | 2/20 (10%) | 4/47 (8.5%) | 3/47 (6.4%) | 1/6 (16.7%) | |||||
| Anal inflammation | 2/33 (6.1%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Ascites | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Autoimmune colitis | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Breath odour | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Colitis | 0/33 (0%) | 0/20 (0%) | 2/47 (4.3%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Constipation | 9/33 (27.3%) | 8/20 (40%) | 14/47 (29.8%) | 14/47 (29.8%) | 2/6 (33.3%) | |||||
| Defaecation urgency | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Dental caries | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Diarrhoea | 21/33 (63.6%) | 14/20 (70%) | 12/47 (25.5%) | 25/47 (53.2%) | 5/6 (83.3%) | |||||
| Dry mouth | 11/33 (33.3%) | 2/20 (10%) | 5/47 (10.6%) | 8/47 (17%) | 1/6 (16.7%) | |||||
| Duodenitis | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Dyspepsia | 11/33 (33.3%) | 5/20 (25%) | 6/47 (12.8%) | 1/47 (2.1%) | 2/6 (33.3%) | |||||
| Dysphagia | 2/33 (6.1%) | 3/20 (15%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Flatulence | 6/33 (18.2%) | 1/20 (5%) | 5/47 (10.6%) | 3/47 (6.4%) | 2/6 (33.3%) | |||||
| Gastritis | 3/33 (9.1%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Gastrooesophageal reflux disease | 9/33 (27.3%) | 3/20 (15%) | 4/47 (8.5%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Glossodynia | 4/33 (12.1%) | 0/20 (0%) | 0/47 (0%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Haematochezia | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Haemorrhoids | 1/33 (3%) | 0/20 (0%) | 2/47 (4.3%) | 3/47 (6.4%) | 0/6 (0%) | |||||
| Mouth ulceration | 1/33 (3%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Nausea | 20/33 (60.6%) | 16/20 (80%) | 19/47 (40.4%) | 26/47 (55.3%) | 4/6 (66.7%) | |||||
| Oral pain | 5/33 (15.2%) | 4/20 (20%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Paraesthesia oral | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Stomatitis | 8/33 (24.2%) | 2/20 (10%) | 7/47 (14.9%) | 0/47 (0%) | 2/6 (33.3%) | |||||
| Toothache | 2/33 (6.1%) | 2/20 (10%) | 3/47 (6.4%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Vomiting | 10/33 (30.3%) | 9/20 (45%) | 15/47 (31.9%) | 14/47 (29.8%) | 3/6 (50%) | |||||
| Retching | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| General disorders | ||||||||||
| Asthenia | 0/33 (0%) | 1/20 (5%) | 3/47 (6.4%) | 4/47 (8.5%) | 1/6 (16.7%) | |||||
| Chest discomfort | 3/33 (9.1%) | 2/20 (10%) | 2/47 (4.3%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Chest pain | 0/33 (0%) | 3/20 (15%) | 5/47 (10.6%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Chills | 8/33 (24.2%) | 6/20 (30%) | 13/47 (27.7%) | 9/47 (19.1%) | 3/6 (50%) | |||||
| Face oedema | 4/33 (12.1%) | 0/20 (0%) | 1/47 (2.1%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Fatigue | 29/33 (87.9%) | 15/20 (75%) | 31/47 (66%) | 35/47 (74.5%) | 6/6 (100%) | |||||
| Generalised oedema | 2/33 (6.1%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Influenza like illness | 3/33 (9.1%) | 0/20 (0%) | 2/47 (4.3%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Localised oedema | 1/33 (3%) | 1/20 (5%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Malaise | 2/33 (6.1%) | 2/20 (10%) | 1/47 (2.1%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Mucosal inflammation | 11/33 (33.3%) | 5/20 (25%) | 2/47 (4.3%) | 4/47 (8.5%) | 1/6 (16.7%) | |||||
| Non-cardiac chest pain | 1/33 (3%) | 0/20 (0%) | 2/47 (4.3%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Oedema | 1/33 (3%) | 1/20 (5%) | 2/47 (4.3%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Oedema peripheral | 11/33 (33.3%) | 5/20 (25%) | 12/47 (25.5%) | 13/47 (27.7%) | 3/6 (50%) | |||||
| Pain | 0/33 (0%) | 2/20 (10%) | 2/47 (4.3%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Pyrexia | 10/33 (30.3%) | 7/20 (35%) | 18/47 (38.3%) | 11/47 (23.4%) | 6/6 (100%) | |||||
| Sensation of foreign body | 2/33 (6.1%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Temperature intolerance | 2/33 (6.1%) | 1/20 (5%) | 2/47 (4.3%) | 0/47 (0%) | 0/6 (0%) | |||||
| Hepatobiliary disorders | ||||||||||
| Autoimmune hepatitis | 0/33 (0%) | 1/20 (5%) | 2/47 (4.3%) | 0/47 (0%) | 0/6 (0%) | |||||
| Immune system disorders | ||||||||||
| Anaphylactic reaction | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Infections and infestations | ||||||||||
| Bronchitis | 3/33 (9.1%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Clostridium difficile infection | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Ear infection | 0/33 (0%) | 1/20 (5%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Gingivitis | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Groin abscess | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Infected bite | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Lung infection | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Pneumonia | 1/33 (3%) | 2/20 (10%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Post procedural infection | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Rhinitis | 2/33 (6.1%) | 1/20 (5%) | 1/47 (2.1%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Sinusitis | 1/33 (3%) | 1/20 (5%) | 4/47 (8.5%) | 3/47 (6.4%) | 0/6 (0%) | |||||
| Skin infection | 1/33 (3%) | 1/20 (5%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Tinea infection | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Tooth infection | 3/33 (9.1%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Upper respiratory tract infection | 8/33 (24.2%) | 7/20 (35%) | 9/47 (19.1%) | 7/47 (14.9%) | 0/6 (0%) | |||||
| Urinary tract infection | 1/33 (3%) | 2/20 (10%) | 2/47 (4.3%) | 3/47 (6.4%) | 2/6 (33.3%) | |||||
| Vulvitis | 0/33 (0%) | 0/20 (0%) | 2/47 (4.3%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Cellulitis | 0/33 (0%) | 1/20 (5%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Genital infection fungal | 1/33 (3%) | 1/20 (5%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Pharyngitis | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Ankle fracture | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Contusion | 5/33 (15.2%) | 0/20 (0%) | 2/47 (4.3%) | 3/47 (6.4%) | 0/6 (0%) | |||||
| Fall | 1/33 (3%) | 1/20 (5%) | 2/47 (4.3%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Fracture | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Infusion related reaction | 0/33 (0%) | 1/20 (5%) | 5/47 (10.6%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Laceration | 0/33 (0%) | 0/20 (0%) | 3/47 (6.4%) | 0/47 (0%) | 0/6 (0%) | |||||
| Post procedural complication | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Procedural pain | 0/33 (0%) | 3/20 (15%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Skin abrasion | 2/33 (6.1%) | 1/20 (5%) | 3/47 (6.4%) | 3/47 (6.4%) | 0/6 (0%) | |||||
| Sunburn | 0/33 (0%) | 1/20 (5%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Investigations | ||||||||||
| Alanine aminotransferase increased | 13/33 (39.4%) | 5/20 (25%) | 8/47 (17%) | 16/47 (34%) | 3/6 (50%) | |||||
| Amylase increased | 5/33 (15.2%) | 0/20 (0%) | 4/47 (8.5%) | 8/47 (17%) | 2/6 (33.3%) | |||||
| Aspartate aminotransferase increased | 12/33 (36.4%) | 6/20 (30%) | 9/47 (19.1%) | 14/47 (29.8%) | 3/6 (50%) | |||||
| Blood alkaline phosphatase increased | 5/33 (15.2%) | 3/20 (15%) | 2/47 (4.3%) | 4/47 (8.5%) | 0/6 (0%) | |||||
| Blood bilirubin increased | 1/33 (3%) | 0/20 (0%) | 2/47 (4.3%) | 3/47 (6.4%) | 1/6 (16.7%) | |||||
| Blood cholesterol increased | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Blood creatinine increased | 12/33 (36.4%) | 2/20 (10%) | 7/47 (14.9%) | 9/47 (19.1%) | 2/6 (33.3%) | |||||
| Gamma-glutamyltransferase increased | 2/33 (6.1%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Lipase increased | 2/33 (6.1%) | 0/20 (0%) | 11/47 (23.4%) | 19/47 (40.4%) | 2/6 (33.3%) | |||||
| Lymphocyte count decreased | 9/33 (27.3%) | 1/20 (5%) | 1/47 (2.1%) | 4/47 (8.5%) | 1/6 (16.7%) | |||||
| Neutrophil count decreased | 6/33 (18.2%) | 0/20 (0%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Platelet count decreased | 6/33 (18.2%) | 0/20 (0%) | 3/47 (6.4%) | 0/47 (0%) | 0/6 (0%) | |||||
| Weight decreased | 4/33 (12.1%) | 4/20 (20%) | 5/47 (10.6%) | 11/47 (23.4%) | 4/6 (66.7%) | |||||
| Weight increased | 3/33 (9.1%) | 0/20 (0%) | 7/47 (14.9%) | 4/47 (8.5%) | 1/6 (16.7%) | |||||
| White blood cell count decreased | 7/33 (21.2%) | 1/20 (5%) | 1/47 (2.1%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 16/33 (48.5%) | 11/20 (55%) | 13/47 (27.7%) | 19/47 (40.4%) | 5/6 (83.3%) | |||||
| Dehydration | 7/33 (21.2%) | 6/20 (30%) | 7/47 (14.9%) | 9/47 (19.1%) | 1/6 (16.7%) | |||||
| Diabetes mellitus | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Gout | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Hypercalcaemia | 0/33 (0%) | 2/20 (10%) | 4/47 (8.5%) | 5/47 (10.6%) | 1/6 (16.7%) | |||||
| Hyperglycaemia | 8/33 (24.2%) | 4/20 (20%) | 7/47 (14.9%) | 8/47 (17%) | 1/6 (16.7%) | |||||
| Hyperkalaemia | 3/33 (9.1%) | 2/20 (10%) | 5/47 (10.6%) | 4/47 (8.5%) | 0/6 (0%) | |||||
| Hyperphosphataemia | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Hyperuricaemia | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Hypoalbuminaemia | 3/33 (9.1%) | 0/20 (0%) | 1/47 (2.1%) | 5/47 (10.6%) | 2/6 (33.3%) | |||||
| Hypocalcaemia | 3/33 (9.1%) | 2/20 (10%) | 1/47 (2.1%) | 4/47 (8.5%) | 1/6 (16.7%) | |||||
| Hypoglycaemia | 0/33 (0%) | 2/20 (10%) | 0/47 (0%) | 3/47 (6.4%) | 0/6 (0%) | |||||
| Hypokalaemia | 1/33 (3%) | 1/20 (5%) | 3/47 (6.4%) | 4/47 (8.5%) | 1/6 (16.7%) | |||||
| Hypomagnesaemia | 3/33 (9.1%) | 5/20 (25%) | 3/47 (6.4%) | 6/47 (12.8%) | 1/6 (16.7%) | |||||
| Hyponatraemia | 9/33 (27.3%) | 1/20 (5%) | 6/47 (12.8%) | 6/47 (12.8%) | 1/6 (16.7%) | |||||
| Hypophagia | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Hypophosphataemia | 3/33 (9.1%) | 2/20 (10%) | 3/47 (6.4%) | 6/47 (12.8%) | 0/6 (0%) | |||||
| Polydipsia | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 12/33 (36.4%) | 9/20 (45%) | 24/47 (51.1%) | 12/47 (25.5%) | 5/6 (83.3%) | |||||
| Arthritis | 1/33 (3%) | 1/20 (5%) | 1/47 (2.1%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Back pain | 7/33 (21.2%) | 6/20 (30%) | 15/47 (31.9%) | 8/47 (17%) | 1/6 (16.7%) | |||||
| Costochondritis | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Flank pain | 1/33 (3%) | 2/20 (10%) | 8/47 (17%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Joint range of motion decreased | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Joint swelling | 1/33 (3%) | 1/20 (5%) | 1/47 (2.1%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Lower extremity mass | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Muscle spasms | 4/33 (12.1%) | 5/20 (25%) | 3/47 (6.4%) | 4/47 (8.5%) | 3/6 (50%) | |||||
| Muscle twitching | 0/33 (0%) | 2/20 (10%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Muscular weakness | 2/33 (6.1%) | 2/20 (10%) | 3/47 (6.4%) | 6/47 (12.8%) | 2/6 (33.3%) | |||||
| Musculoskeletal chest pain | 2/33 (6.1%) | 5/20 (25%) | 6/47 (12.8%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Musculoskeletal pain | 2/33 (6.1%) | 4/20 (20%) | 3/47 (6.4%) | 5/47 (10.6%) | 2/6 (33.3%) | |||||
| Musculoskeletal stiffness | 2/33 (6.1%) | 0/20 (0%) | 1/47 (2.1%) | 4/47 (8.5%) | 0/6 (0%) | |||||
| Myalgia | 10/33 (30.3%) | 5/20 (25%) | 11/47 (23.4%) | 10/47 (21.3%) | 4/6 (66.7%) | |||||
| Neck pain | 0/33 (0%) | 2/20 (10%) | 8/47 (17%) | 0/47 (0%) | 0/6 (0%) | |||||
| Osteoarthritis | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Osteonecrosis of jaw | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Pain in extremity | 12/33 (36.4%) | 6/20 (30%) | 8/47 (17%) | 5/47 (10.6%) | 2/6 (33.3%) | |||||
| Pain in jaw | 1/33 (3%) | 1/20 (5%) | 2/47 (4.3%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Myopathy | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Nervous system disorders | ||||||||||
| Ataxia | 1/33 (3%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Carpal tunnel syndrome | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Cerebellar syndrome | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Cognitive disorder | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 3/47 (6.4%) | 1/6 (16.7%) | |||||
| Disturbance in attention | 2/33 (6.1%) | 0/20 (0%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Dizziness | 11/33 (33.3%) | 3/20 (15%) | 10/47 (21.3%) | 12/47 (25.5%) | 2/6 (33.3%) | |||||
| Dysgeusia | 21/33 (63.6%) | 10/20 (50%) | 5/47 (10.6%) | 8/47 (17%) | 1/6 (16.7%) | |||||
| Epilepsy | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Headache | 13/33 (39.4%) | 5/20 (25%) | 15/47 (31.9%) | 13/47 (27.7%) | 4/6 (66.7%) | |||||
| Hyperaesthesia | 1/33 (3%) | 2/20 (10%) | 0/47 (0%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Neuropathy peripheral | 4/33 (12.1%) | 2/20 (10%) | 1/47 (2.1%) | 3/47 (6.4%) | 0/6 (0%) | |||||
| Paraesthesia | 1/33 (3%) | 1/20 (5%) | 4/47 (8.5%) | 3/47 (6.4%) | 2/6 (33.3%) | |||||
| Peripheral sensory neuropathy | 1/33 (3%) | 1/20 (5%) | 0/47 (0%) | 3/47 (6.4%) | 0/6 (0%) | |||||
| Restless legs syndrome | 1/33 (3%) | 1/20 (5%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Sciatica | 0/33 (0%) | 0/20 (0%) | 1/47 (2.1%) | 3/47 (6.4%) | 1/6 (16.7%) | |||||
| Seizure | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Somnolence | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Speech disorder | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Syncope | 1/33 (3%) | 1/20 (5%) | 2/47 (4.3%) | 0/47 (0%) | 0/6 (0%) | |||||
| Tremor | 0/33 (0%) | 1/20 (5%) | 3/47 (6.4%) | 2/47 (4.3%) | 2/6 (33.3%) | |||||
| Psychiatric disorders | ||||||||||
| Anxiety | 3/33 (9.1%) | 2/20 (10%) | 7/47 (14.9%) | 4/47 (8.5%) | 1/6 (16.7%) | |||||
| Confusional state | 2/33 (6.1%) | 0/20 (0%) | 2/47 (4.3%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Depression | 4/33 (12.1%) | 0/20 (0%) | 1/47 (2.1%) | 2/47 (4.3%) | 2/6 (33.3%) | |||||
| Insomnia | 5/33 (15.2%) | 4/20 (20%) | 9/47 (19.1%) | 9/47 (19.1%) | 3/6 (50%) | |||||
| Irritability | 1/33 (3%) | 1/20 (5%) | 0/47 (0%) | 3/47 (6.4%) | 1/6 (16.7%) | |||||
| Mental status changes | 0/33 (0%) | 0/20 (0%) | 2/47 (4.3%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Libido decreased | 2/33 (6.1%) | 0/20 (0%) | 0/47 (0%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Acute kidney injury | 3/33 (9.1%) | 1/20 (5%) | 1/47 (2.1%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Azotaemia | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Haematuria | 1/33 (3%) | 2/20 (10%) | 1/47 (2.1%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Nocturia | 0/33 (0%) | 1/20 (5%) | 1/47 (2.1%) | 3/47 (6.4%) | 0/6 (0%) | |||||
| Pollakiuria | 1/33 (3%) | 2/20 (10%) | 1/47 (2.1%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Polyuria | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Proteinuria | 4/33 (12.1%) | 1/20 (5%) | 3/47 (6.4%) | 6/47 (12.8%) | 2/6 (33.3%) | |||||
| Urinary retention | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Breast mass | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Erectile dysfunction | 0/33 (0%) | 1/20 (5%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Testicular pain | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 18/33 (54.5%) | 13/20 (65%) | 24/47 (51.1%) | 14/47 (29.8%) | 5/6 (83.3%) | |||||
| Dysphonia | 4/33 (12.1%) | 5/20 (25%) | 7/47 (14.9%) | 4/47 (8.5%) | 1/6 (16.7%) | |||||
| Dyspnoea | 12/33 (36.4%) | 4/20 (20%) | 13/47 (27.7%) | 9/47 (19.1%) | 2/6 (33.3%) | |||||
| Dyspnoea at rest | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
| Dyspnoea exertional | 4/33 (12.1%) | 3/20 (15%) | 7/47 (14.9%) | 4/47 (8.5%) | 0/6 (0%) | |||||
| Epistaxis | 6/33 (18.2%) | 2/20 (10%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Haemoptysis | 2/33 (6.1%) | 2/20 (10%) | 2/47 (4.3%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Hiccups | 0/33 (0%) | 1/20 (5%) | 3/47 (6.4%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Hypoxia | 1/33 (3%) | 0/20 (0%) | 3/47 (6.4%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Nasal congestion | 8/33 (24.2%) | 1/20 (5%) | 9/47 (19.1%) | 6/47 (12.8%) | 1/6 (16.7%) | |||||
| Nasal dryness | 3/33 (9.1%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Oropharyngeal pain | 8/33 (24.2%) | 3/20 (15%) | 6/47 (12.8%) | 5/47 (10.6%) | 0/6 (0%) | |||||
| Paranasal sinus hypersecretion | 0/33 (0%) | 1/20 (5%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Pharyngeal inflammation | 1/33 (3%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Pleural effusion | 1/33 (3%) | 0/20 (0%) | 4/47 (8.5%) | 0/47 (0%) | 0/6 (0%) | |||||
| Pleuritic pain | 1/33 (3%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Pneumonitis | 2/33 (6.1%) | 1/20 (5%) | 3/47 (6.4%) | 5/47 (10.6%) | 0/6 (0%) | |||||
| Productive cough | 0/33 (0%) | 0/20 (0%) | 2/47 (4.3%) | 3/47 (6.4%) | 1/6 (16.7%) | |||||
| Pulmonary embolism | 1/33 (3%) | 1/20 (5%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Respiratory tract congestion | 2/33 (6.1%) | 0/20 (0%) | 2/47 (4.3%) | 0/47 (0%) | 0/6 (0%) | |||||
| Rhinitis allergic | 5/33 (15.2%) | 1/20 (5%) | 8/47 (17%) | 0/47 (0%) | 0/6 (0%) | |||||
| Rhinorrhoea | 1/33 (3%) | 1/20 (5%) | 1/47 (2.1%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Sinus congestion | 1/33 (3%) | 1/20 (5%) | 4/47 (8.5%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Sleep apnoea syndrome | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Sneezing | 2/33 (6.1%) | 0/20 (0%) | 1/47 (2.1%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Throat irritation | 0/33 (0%) | 1/20 (5%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Upper-airway cough syndrome | 1/33 (3%) | 1/20 (5%) | 2/47 (4.3%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Wheezing | 1/33 (3%) | 0/20 (0%) | 7/47 (14.9%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Sputum increased | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Alopecia | 1/33 (3%) | 2/20 (10%) | 2/47 (4.3%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Blister | 2/33 (6.1%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Dermatitis acneiform | 1/33 (3%) | 1/20 (5%) | 3/47 (6.4%) | 0/47 (0%) | 0/6 (0%) | |||||
| Dry skin | 11/33 (33.3%) | 3/20 (15%) | 11/47 (23.4%) | 4/47 (8.5%) | 1/6 (16.7%) | |||||
| Dyshidrotic eczema | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Ecchymosis | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Erythema | 3/33 (9.1%) | 2/20 (10%) | 2/47 (4.3%) | 4/47 (8.5%) | 1/6 (16.7%) | |||||
| Hair colour changes | 6/33 (18.2%) | 4/20 (20%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Hair growth abnormal | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Hyperhidrosis | 1/33 (3%) | 2/20 (10%) | 5/47 (10.6%) | 2/47 (4.3%) | 3/6 (50%) | |||||
| Hyperkeratosis | 2/33 (6.1%) | 1/20 (5%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Night sweats | 0/33 (0%) | 1/20 (5%) | 3/47 (6.4%) | 4/47 (8.5%) | 2/6 (33.3%) | |||||
| Palmar-plantar erythrodysaesthesia syndrome | 13/33 (39.4%) | 0/20 (0%) | 1/47 (2.1%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Pruritus | 9/33 (27.3%) | 9/20 (45%) | 18/47 (38.3%) | 21/47 (44.7%) | 3/6 (50%) | |||||
| Pruritus generalised | 0/33 (0%) | 1/20 (5%) | 2/47 (4.3%) | 0/47 (0%) | 0/6 (0%) | |||||
| Psoriasis | 1/33 (3%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Purpura | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Rash | 9/33 (27.3%) | 7/20 (35%) | 18/47 (38.3%) | 15/47 (31.9%) | 4/6 (66.7%) | |||||
| Rash generalised | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Rash macular | 0/33 (0%) | 0/20 (0%) | 3/47 (6.4%) | 2/47 (4.3%) | 0/6 (0%) | |||||
| Rash maculo-papular | 10/33 (30.3%) | 4/20 (20%) | 7/47 (14.9%) | 8/47 (17%) | 0/6 (0%) | |||||
| Rash papular | 0/33 (0%) | 1/20 (5%) | 2/47 (4.3%) | 0/47 (0%) | 0/6 (0%) | |||||
| Rash pruritic | 0/33 (0%) | 1/20 (5%) | 2/47 (4.3%) | 4/47 (8.5%) | 0/6 (0%) | |||||
| Skin discolouration | 3/33 (9.1%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Skin disorder | 2/33 (6.1%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Skin exfoliation | 2/33 (6.1%) | 2/20 (10%) | 2/47 (4.3%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Skin hyperpigmentation | 1/33 (3%) | 0/20 (0%) | 0/47 (0%) | 1/47 (2.1%) | 1/6 (16.7%) | |||||
| Skin lesion | 1/33 (3%) | 1/20 (5%) | 2/47 (4.3%) | 2/47 (4.3%) | 1/6 (16.7%) | |||||
| Skin mass | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Urticaria | 0/33 (0%) | 1/20 (5%) | 3/47 (6.4%) | 0/47 (0%) | 0/6 (0%) | |||||
| Yellow skin | 7/33 (21.2%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Vascular disorders | ||||||||||
| Deep vein thrombosis | 2/33 (6.1%) | 0/20 (0%) | 1/47 (2.1%) | 0/47 (0%) | 0/6 (0%) | |||||
| Flushing | 5/33 (15.2%) | 3/20 (15%) | 3/47 (6.4%) | 6/47 (12.8%) | 1/6 (16.7%) | |||||
| Haematoma | 1/33 (3%) | 1/20 (5%) | 0/47 (0%) | 1/47 (2.1%) | 0/6 (0%) | |||||
| Hot flush | 5/33 (15.2%) | 2/20 (10%) | 3/47 (6.4%) | 4/47 (8.5%) | 0/6 (0%) | |||||
| Hypertension | 17/33 (51.5%) | 8/20 (40%) | 4/47 (8.5%) | 6/47 (12.8%) | 3/6 (50%) | |||||
| Hypotension | 2/33 (6.1%) | 4/20 (20%) | 3/47 (6.4%) | 6/47 (12.8%) | 2/6 (33.3%) | |||||
| Orthostatic hypertension | 0/33 (0%) | 1/20 (5%) | 0/47 (0%) | 0/47 (0%) | 0/6 (0%) | |||||
| Phlebitis | 0/33 (0%) | 0/20 (0%) | 0/47 (0%) | 0/47 (0%) | 1/6 (16.7%) | |||||
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 | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01472081
Other Study ID Numbers:
- CA209-016
First Posted:
Nov 16, 2011
Last Update Posted:
Dec 2, 2021
Last Verified:
Nov 1, 2021