A Study of the Safety and Tolerability of BMS-986183 in Patients With Liver Cancer

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02828124
• Collaborator: (none)
• Enrollment: 25
• Locations: 4
• Arms: 4
• Actual Duration (Months): 16.5
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of BMS-986183 in patients with liver cancer.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Biological: BMS-986183; Biological: Nivolumab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study of BMS-986183 in Subjects With Advanced Hepatocellular Carcinoma
• Actual Study Start Date: Aug 23, 2016
• Actual Primary Completion Date: Jan 8, 2018
• Actual Study Completion Date: Jan 8, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation Monotherapy	Biological: BMS-986183; specified dose on specified days
Experimental: Dose Expansion Monotherapy	Biological: BMS-986183; specified dose on specified days
Experimental: Dose Escalation Combination Therapy	Biological: BMS-986183; specified dose on specified days; Biological: Nivolumab; specified dose on specified days; Other Names: BMS-936558 Opdivo
Experimental: Dose Expansion Combination Therapy	Biological: BMS-986183; specified dose on specified days; Biological: Nivolumab; specified dose on specified days; Other Names: BMS-936558 Opdivo

Outcome Measures

Primary Outcome Measures

1. Incidence of Adverse Events at Its Worst Grade [First dose up to approximately 24 months]

   Evaluated by comparing the incidence of Adverse Events (AEs) among subjects using their assigned treatment for at least one day.

2. Incidence of Serious Adverse Events at Its Worst Grade [First dose up to approximately 24 months]

   Evaluated by comparing the incidence of Serious Adverse Events (SAEs) among subjects using their assigned treatment for at least one day.

3. Incidence of Adverse Events Leading to Discontinuation [First dose up to approximately 24 months]

   Evaluated by comparing the incidence of Adverse Events leading to discontinuation among subjects using their assigned treatment for at least one day.

4. Incidence of Adverse Events Leading to Death [First dose up to approximately 24 months]

   Evaluated by comparing the incidence of Adverse Events leading to death among subjects using their assigned treatment for at least one day.

5. Incidence of Laboratory Test Toxicity Grade Shifting From Baseline [First dose up to approximately 24 months]

Secondary Outcome Measures

1. Best Overall Response (BOR) [First dose up to approximately 24 months]

   Defined as BOR designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy. CR or PR determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met.

2. Overall Response Rate (ORR) [First dose up to approximately 24 months]

   Defined as the total number of subjects whose BOR is either a CR or PR divided by the total number of subjects in the population of interest

3. Duration of Response (DoR) [First dose up to approximately 24 months]

   Defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first. For those subjects who remain alive and have not progressed or received subsequent therapy, DoR will be censored on the date of last tumor assessment

4. Progression Free Survival (PFS) [First dose up to approximately 24 months]

   Defined as the time from the first dose of study drug to the date of the first objective documentation of tumor progression or death due to any cause. Subjects who did not progress nor died will be censored on the date of their last tumor assessment. Subjects who did not have any on-study tumor assessments will be censored on the date of the first dose of study drug.

5. PFS Rate at Week 't' [First dose up to approximately 24 months]

   Defined as the proportion of subjects who remain progression free and surviving at 't' weeks (t=12, 24, 36, etc). The proportion will be calculated by the product-limit method (Kaplan-Meier [K-M] estimate) which takes into account censored data

6. Maximum Observed Concentration (Cmax) [From first does up to approximately 24 months]

   To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Cmax

7. Time of Maximum Observed Concentration (Tmax) [First dose up to approximately 24 months]

   to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Tmax.

8. Area Under the Concentration-time Curve From Time 0 to T of the Last Quantifiable Concentration [AUC(0-T)] [First does up to appromimately 24 months]

   to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AUC(0-T)]

9. Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)] [First dose up to approximately 24 months]

   To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AUC(TAU).

10. Concentration at the End of a Dosing Interval (Ctau) [First dose up to approximately 24 months]

    To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by

11. Trough Observed Concentration, Including Predose Concentrations and Ctau (Ctrough) [First dose up to approximately 24 months]

    to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by (Ctrough)

12. Total Body Clearance (CLT) [First dose to approximately 24 months]

    to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by CLT

13. Apparent Volume of Distribution at Steady-state (Vss) [First dose up to approximately 24 months]

    to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Vss

14. Volume of Distribution of Terminal Phase (Vz) [First dose up to approximately 24 months]

    (to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Vz.

15. Accumulation Index; Ratio of Cmax at Steady-state to Cmax After the First Dose (AI_Cmax) [First dose up to approximately 24 months]

    to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_Cmax.

16. Accumulation Index; Ratio of Ctau at Steady-state to Ctau After the First Dose (AI_Ctau) [First dose up to approximately 24 months]

    to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_Ctau.

17. Accumulation Index; Ratio of AUC(TAU) at Steady-state to AUC(TAU) After the First Dose [AI_AUC(TAU)] [First dose up to approximately 24 months]

    To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_AUC(TAU).

18. Average Concentration Over a Dosing Interval Calculated by Dividing AUC(TAU) at Steady State by Tau (Css,Ave) [First dose up to approximately 24 months]

    To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Css,avg.

19. Terminal Half-life (T-HALF) [First dose up to approximately 24 months]

    to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by T-HALF.

20. Changes in QTcF (ΔQTcF) From Baseline [Baseline up to approximately 24 months]

    To assess the effect of dosage regimen and exposure [active ADC and unconjugated tubulysin] of BMS-986183 as monotherapy on the QT interval.

21. Incidence of Positive Anti-drug Antibody (ADA) [First dose up to approximately 24 months]

    The immunogenicity of BMS-986183 (as monotherapy and in combination with nivolumab) will be measured by assessment of the presence or absence of specific ADA to BMS-986183. The incidence of positive ADA will be calculated.

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:

• Must have advanced liver cancer that cannot be treated with surgery or other local methods

• Liver cancer is confirmed by a microscopic examination of tissue

• Liver disease is classified as 'A' by a standard method called Child-Pugh score

• Daily living abilities are classified as '0 or 1' by a standard method from the Eastern Cooperative Oncology Group (ECOG)

• Women must use contraception

Exclusion Criteria:

• Prior liver transplant

• Increase in blood pressure in some of the veins entering the liver

• Cancer that has spread to the brain or the layers of tissue that cover the brain or spinal cord

• Infection with both hepatitis B and C, both hepatitis D and B, infection with HIV, or other infections

• Disease of the heart or blood vessels around the heart

• Active cancers within the last 2 years

• No more than 2 prior systemic treatments or other investigational agents except PD-1/PD-L1 or Ipilimumab (Part 2)

• Currently on anti-platelet or anti-coagulation therapy

• Radiotherapy within 4 weeks of treatment

• Any major allergies

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Ottawa	Ontario	Canada	K1H 8L6
2	Local Institution	Seoul		Korea, Republic of	05505
3	Local Institution	Singapore		Singapore	169610
4	Local Institution	Taipei		Taiwan	10048

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol - May 3, 2017
• Statistical Analysis Plan - Aug 21, 2017

More Information

Additional Information:

• BMS Clinical Trial Patient Recruiting

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02828124
• Other Study ID Numbers: CA015-003
• First Posted: Jul 11, 2016
• Last Update Posted: Jan 30, 2019
• Last Verified: Jan 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Nivolumab

Study Results

Participant Flow

Recruitment Details	There were 10 subjects were treated in this study. All 10 subjects were enrolled in BMS-986183 escalation (Part 1)

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Period Title: Overall Study
STARTED	1	2	1	6
COMPLETED	0	0	0	0
NOT COMPLETED	1	2	1	6

Baseline Characteristics

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg	Total
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Total of all reporting groups
Overall Participants	1	2	1	6	10
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.0 (NA)	67.5 (4.9)	57.0 (NA)	49.5 (8.6)	54.5 (10.0)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	1 16.7%	1 10%
Male	1 100%	2 100%	1 100%	5 83.3%	9 90%
Race/Ethnicity, Customized (Count of Participants)
White	0 0%	0 0%	0 0%	1 16.7%	1 10%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 100%	2 100%	1 100%	5 83.3%	9 90%

Outcome Measures

1. Primary Outcome

Title	Incidence of Adverse Events at Its Worst Grade
Description	Evaluated by comparing the incidence of Adverse Events (AEs) among subjects using their assigned treatment for at least one day.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

2. Primary Outcome

Title	Incidence of Serious Adverse Events at Its Worst Grade
Description	Evaluated by comparing the incidence of Serious Adverse Events (SAEs) among subjects using their assigned treatment for at least one day.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

3. Primary Outcome

Title	Incidence of Adverse Events Leading to Discontinuation
Description	Evaluated by comparing the incidence of Adverse Events leading to discontinuation among subjects using their assigned treatment for at least one day.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

4. Primary Outcome

Title	Incidence of Adverse Events Leading to Death
Description	Evaluated by comparing the incidence of Adverse Events leading to death among subjects using their assigned treatment for at least one day.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

5. Primary Outcome

Title	Incidence of Laboratory Test Toxicity Grade Shifting From Baseline
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

6. Secondary Outcome

Title	Best Overall Response (BOR)
Description	Defined as BOR designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy. CR or PR determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

7. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Defined as the total number of subjects whose BOR is either a CR or PR divided by the total number of subjects in the population of interest
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

8. Secondary Outcome

Title	Duration of Response (DoR)
Description	Defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first. For those subjects who remain alive and have not progressed or received subsequent therapy, DoR will be censored on the date of last tumor assessment
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

9. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Defined as the time from the first dose of study drug to the date of the first objective documentation of tumor progression or death due to any cause. Subjects who did not progress nor died will be censored on the date of their last tumor assessment. Subjects who did not have any on-study tumor assessments will be censored on the date of the first dose of study drug.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

10. Secondary Outcome

Title	PFS Rate at Week 't'
Description	Defined as the proportion of subjects who remain progression free and surviving at 't' weeks (t=12, 24, 36, etc). The proportion will be calculated by the product-limit method (Kaplan-Meier [K-M] estimate) which takes into account censored data
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

11. Secondary Outcome

Title	Maximum Observed Concentration (Cmax)
Description	To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Cmax
Time Frame	From first does up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

12. Secondary Outcome

Title	Time of Maximum Observed Concentration (Tmax)
Description	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Tmax.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

13. Secondary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to T of the Last Quantifiable Concentration [AUC(0-T)]
Description	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AUC(0-T)]
Time Frame	First does up to appromimately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

14. Secondary Outcome

Title	Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)]
Description	To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AUC(TAU).
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

15. Secondary Outcome

Title	Concentration at the End of a Dosing Interval (Ctau)
Description	To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

16. Secondary Outcome

Title	Trough Observed Concentration, Including Predose Concentrations and Ctau (Ctrough)
Description	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by (Ctrough)
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

17. Secondary Outcome

Title	Total Body Clearance (CLT)
Description	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by CLT
Time Frame	First dose to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

18. Secondary Outcome

Title	Apparent Volume of Distribution at Steady-state (Vss)
Description	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Vss
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

19. Secondary Outcome

Title	Volume of Distribution of Terminal Phase (Vz)
Description	(to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Vz.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

20. Secondary Outcome

Title	Accumulation Index; Ratio of Cmax at Steady-state to Cmax After the First Dose (AI_Cmax)
Description	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_Cmax.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

21. Secondary Outcome

Title	Accumulation Index; Ratio of Ctau at Steady-state to Ctau After the First Dose (AI_Ctau)
Description	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_Ctau.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

22. Secondary Outcome

Title	Accumulation Index; Ratio of AUC(TAU) at Steady-state to AUC(TAU) After the First Dose [AI_AUC(TAU)]
Description	To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_AUC(TAU).
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

23. Secondary Outcome

Title	Average Concentration Over a Dosing Interval Calculated by Dividing AUC(TAU) at Steady State by Tau (Css,Ave)
Description	To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Css,avg.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

24. Secondary Outcome

Title	Terminal Half-life (T-HALF)
Description	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by T-HALF.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

25. Secondary Outcome

Title	Changes in QTcF (ΔQTcF) From Baseline
Description	To assess the effect of dosage regimen and exposure [active ADC and unconjugated tubulysin] of BMS-986183 as monotherapy on the QT interval.
Time Frame	Baseline up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

26. Secondary Outcome

Title	Incidence of Positive Anti-drug Antibody (ADA)
Description	The immunogenicity of BMS-986183 (as monotherapy and in combination with nivolumab) will be measured by assessment of the presence or absence of specific ADA to BMS-986183. The incidence of positive ADA will be calculated.
Time Frame	First dose up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The study was terminated and data is not reported for privacy reasons.

Arm/Group Title	BMS-986183 3 mg	BMS-986183 9 mg	BMS-986183 18 mg	BMS-986183 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab	Dose escalation in combination with Nivolumab
Measure Participants	0	0	0	0

Adverse Events

Time Frame	First dose up to approximately 24 months
Arm/Group Title	BMS-986183 ESC 3 mg		BMS-986183 ESC 9 mg		BMS-986183 ESC 18 mg		BMS-986183 ESC 36 mg
Arm/Group Description	Dose escalation in combination with Nivolumab		Dose escalation in combination with Nivolumab		Dose escalation in combination with Nivolumab		Dose escalation in combination with Nivolumab
All Cause Mortality
	BMS-986183 ESC 3 mg		BMS-986183 ESC 9 mg		BMS-986183 ESC 18 mg		BMS-986183 ESC 36 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		2/2 (100%)		0/1 (0%)		5/6 (83.3%)
Serious Adverse Events
	BMS-986183 ESC 3 mg		BMS-986183 ESC 9 mg		BMS-986183 ESC 18 mg		BMS-986183 ESC 36 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		1/2 (50%)		1/1 (100%)		2/6 (33.3%)
Gastrointestinal disorders
Oesophageal varices haemorrhage	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Hepatobiliary disorders
Hepatic failure	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Infections and infestations
Gastroenteritis	0/1 (0%)		1/2 (50%)		0/1 (0%)		0/6 (0%)
Lung infection	0/1 (0%)		0/2 (0%)		1/1 (100%)		0/6 (0%)
Upper respiratory tract infection	0/1 (0%)		0/2 (0%)		1/1 (100%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Malignant neoplasm progression	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Other (Not Including Serious) Adverse Events
	BMS-986183 ESC 3 mg		BMS-986183 ESC 9 mg		BMS-986183 ESC 18 mg		BMS-986183 ESC 36 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		2/2 (100%)		1/1 (100%)		5/6 (83.3%)
Cardiac disorders
Palpitations	0/1 (0%)		0/2 (0%)		1/1 (100%)		0/6 (0%)
Gastrointestinal disorders
Abdominal distension	0/1 (0%)		1/2 (50%)		1/1 (100%)		0/6 (0%)
Abdominal pain	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Ascites	0/1 (0%)		0/2 (0%)		0/1 (0%)		2/6 (33.3%)
Constipation	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Diarrhoea	0/1 (0%)		0/2 (0%)		1/1 (100%)		1/6 (16.7%)
Nausea	0/1 (0%)		0/2 (0%)		1/1 (100%)		1/6 (16.7%)
Vomiting	0/1 (0%)		0/2 (0%)		1/1 (100%)		1/6 (16.7%)
General disorders
Fatigue	1/1 (100%)		1/2 (50%)		1/1 (100%)		3/6 (50%)
Pain	0/1 (0%)		0/2 (0%)		1/1 (100%)		0/6 (0%)
Pyrexia	0/1 (0%)		1/2 (50%)		0/1 (0%)		0/6 (0%)
Hepatobiliary disorders
Portal hypertension	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Infections and infestations
Upper respiratory tract infection	0/1 (0%)		0/2 (0%)		1/1 (100%)		0/6 (0%)
Injury, poisoning and procedural complications
Fall	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Investigations
Alanine aminotransferase increased	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Aspartate aminotransferase increased	0/1 (0%)		1/2 (50%)		0/1 (0%)		2/6 (33.3%)
Blood bilirubin increased	0/1 (0%)		0/2 (0%)		0/1 (0%)		2/6 (33.3%)
Weight decreased	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Metabolism and nutrition disorders
Decreased appetite	0/1 (0%)		1/2 (50%)		1/1 (100%)		3/6 (50%)
Dehydration	0/1 (0%)		1/2 (50%)		0/1 (0%)		1/6 (16.7%)
Hyperkalaemia	0/1 (0%)		2/2 (100%)		0/1 (0%)		0/6 (0%)
Hypokalaemia	0/1 (0%)		0/2 (0%)		1/1 (100%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/1 (100%)		0/2 (0%)		1/1 (100%)		1/6 (16.7%)
Musculoskeletal chest pain	0/1 (0%)		1/2 (50%)		0/1 (0%)		0/6 (0%)
Nervous system disorders
Dizziness	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Dysgeusia	0/1 (0%)		1/2 (50%)		0/1 (0%)		0/6 (0%)
Psychiatric disorders
Insomnia	0/1 (0%)		0/2 (0%)		0/1 (0%)		2/6 (33.3%)
Respiratory, thoracic and mediastinal disorders
Cough	0/1 (0%)		1/2 (50%)		1/1 (100%)		1/6 (16.7%)
Dyspnoea	0/1 (0%)		1/2 (50%)		0/1 (0%)		2/6 (33.3%)
Haemoptysis	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Hiccups	0/1 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)
Skin and subcutaneous tissue disorders
Pruritus	0/1 (0%)		1/2 (50%)		1/1 (100%)		0/6 (0%)
Rash generalised	0/1 (0%)		0/2 (0%)		1/1 (100%)		0/6 (0%)
Rash pruritic	0/1 (0%)		0/2 (0%)		1/1 (100%)		0/6 (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