Trial Outcomes & Findings for An Investigational Immuno-Therapy Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Renal Cell Carcinoma (NCT NCT03029780)

NCT ID: NCT03029780

Last Updated: 2022-06-29

Results Overview

The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction broad scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 104 participants
• Primary outcome timeframe: From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)
• Results posted on: 2022-06-29

Participant Flow

104 participants were randomized and treated

Participant milestones

Measure	Arm A: Fixed Ratio Combination Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
Overall Study STARTED	52	52
Overall Study COMPLETED	1	1
Overall Study NOT COMPLETED	51	51

Reasons for withdrawal

Measure	Arm A: Fixed Ratio Combination Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
Overall Study Disease Progression	20	22
Overall Study Study Drug Toxicity	15	11
Overall Study Adverse Event Unrelated to Study Drug	2	3
Overall Study Participant request to discontinue study treatment	4	1
Overall Study Maximum clinical benefit	1	0
Overall Study Participant no longer meets study criteria	0	1
Overall Study Other reasons	6	6
Overall Study Not reported	1	1
Overall Study Death	2	6

Baseline Characteristics

All treated participants

Baseline characteristics by cohort

Measure	Arm A: Fixed Ratio Combination n=52 Participants Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination n=52 Participants Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Total n=104 Participants Total of all reporting groups
Age, Continuous	62.2 Years STANDARD_DEVIATION 10.9 • n=5 Participants • All treated participants	62.6 Years STANDARD_DEVIATION 9.9 • n=7 Participants • All treated participants	62.4 Years STANDARD_DEVIATION 10.4 • n=5 Participants • All treated participants
Sex: Female, Male Female	10 Participants n=5 Participants • All treated participants	14 Participants n=7 Participants • All treated participants	24 Participants n=5 Participants • All treated participants
Sex: Female, Male Male	42 Participants n=5 Participants • All treated participants	38 Participants n=7 Participants • All treated participants	80 Participants n=5 Participants • All treated participants
Race/Ethnicity, Customized White	46 Count of participants n=5 Participants • All treated participants	51 Count of participants n=7 Participants • All treated participants	97 Count of participants n=5 Participants • All treated participants
Race/Ethnicity, Customized Black or African American	1 Count of participants n=5 Participants • All treated participants	0 Count of participants n=7 Participants • All treated participants	1 Count of participants n=5 Participants • All treated participants
Race/Ethnicity, Customized Asian	3 Count of participants n=5 Participants • All treated participants	0 Count of participants n=7 Participants • All treated participants	3 Count of participants n=5 Participants • All treated participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Count of participants n=5 Participants • All treated participants	0 Count of participants n=7 Participants • All treated participants	0 Count of participants n=5 Participants • All treated participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Count of participants n=5 Participants • All treated participants	0 Count of participants n=7 Participants • All treated participants	1 Count of participants n=5 Participants • All treated participants
Race/Ethnicity, Customized Other	1 Count of participants n=5 Participants • All treated participants	1 Count of participants n=7 Participants • All treated participants	2 Count of participants n=5 Participants • All treated participants

PRIMARY outcome

Timeframe: From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)

Population: All treated participants

The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction broad scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).

Outcome measures

Measure	Arm A: Fixed Ratio Combination n=52 Participants Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination n=52 Participants Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
The Percentage of Participant With Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Within 2 Days After Any Dose in the Combination Period	11.5 Percentage of Participants Interval 4.4 to 23.4	11.5 Percentage of Participants Interval 4.4 to 23.4

SECONDARY outcome

Timeframe: From randomization to 2 days following any dose in the combination period (assessed up to November 24th, 2017, approximately 9 months)

Population: All treated participants

The percentage of participants who experienced at least 1 adverse event in the MedDRA Anaphylactic Reaction narrow scope SMQ with onset on the day of or within 2 days after any study therapy infusion during the combination period (Part 1).

Outcome measures

Measure	Arm A: Fixed Ratio Combination n=52 Participants Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination n=52 Participants Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
The Percentage of Participant With Adverse Events in the Narrow Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ) Occurring Within 2 Days After Any Dose in the Combination Period	0 Percentage of Participants Interval 0.0 to 6.8	0 Percentage of Participants Interval 0.0 to 6.8

SECONDARY outcome

Timeframe: From first dose to 30 days after last dose of study therapy (up to approximately 48 months)

Population: All treated participants

The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher, judged to be related to study treatment by the investigator, with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria.

Outcome measures

Measure	Arm A: Fixed Ratio Combination n=52 Participants Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination n=52 Participants Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
The Percentage of Participants With Drug Related Grade 3-5 Adverse Events	48.1 Percentage of Participants Interval 34.0 to 62.4	42.3 Percentage of Participants Interval 28.7 to 56.8

SECONDARY outcome

Timeframe: From first dose to 30 days after last dose of study therapy (up to approximately 48 months)

Population: All treated participants

The percentage of participants who experienced at least 1 adverse event of Grade 3 or higher with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment. Evaluated using the NCI CTCAE version 4.0 criteria

Outcome measures

Measure	Arm A: Fixed Ratio Combination n=52 Participants Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination n=52 Participants Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
The Percentage of Participants With All Causality Grade 3-5 Adverse Events	73.1 Percentage of Particpants Interval 59.0 to 84.4	65.4 Percentage of Particpants Interval 50.9 to 78.0

SECONDARY outcome

Timeframe: From randomization to the date of objectively documented progression or the date of first subsequent anti-cancer (up to approximately 52 months)

Population: All treated participants

The percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of first subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment. Complete Response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10mm. Partial Response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Measure	Arm A: Fixed Ratio Combination n=52 Participants Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination n=52 Participants Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
Objective Response Rate (ORR)	50.0 Percentage of Particpants Interval 35.8 to 64.2	32.7 Percentage of Particpants Interval 20.3 to 47.1

SECONDARY outcome

Timeframe: From randomization to the first date of documented progression or death due to any cause (up to approximately 52 months)

Population: All treated participants

The time between the date of randomization and the first date of documented progression, or death due to any cause, whichever occurs first (per investigator). Participants who die without progression will be considered to have progressed on the date of their death. Participants who did not progress or die are censored on the date of their last evaluable tumor assessment. Participants with no on study tumor assessments and who did not die will be censored on their date of randomization. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the first subsequent anti-cancer therapy. Progression is defined as at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)

Outcome measures

Measure	Arm A: Fixed Ratio Combination n=52 Participants Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination n=52 Participants Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
Progression Free Survival (PFS)	12.06 Months Interval 9.92 to 18.23	7.69 Months Interval 3.42 to 11.33

SECONDARY outcome

Timeframe: pre-dose on day 1 of cycle 2 and 4

Population: All treated participants with available serum time-concentration data

Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized prior to the next dose (predose). 1 Cycle = 3 weeks

Outcome measures

Measure	Arm A: Fixed Ratio Combination n=50 Participants Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination n=46 Participants Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab Ipilimumab - Cycle 2 Day 1	3.92 ug/mL Geometric Coefficient of Variation 28.9	3.43 ug/mL Geometric Coefficient of Variation 43.1
Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab Ipilimumab - Cycle 4 Day 1	5.90 ug/mL Geometric Coefficient of Variation 37.8	5.39 ug/mL Geometric Coefficient of Variation 39.8
Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab Nivolumab - Cycle 2 Day 1	16.2 ug/mL Geometric Coefficient of Variation 29.1	16.1 ug/mL Geometric Coefficient of Variation 46.3
Geometric Mean Trough Concentrations of Nivolumab and Ipilimumab Nivolumab - Cycle 4 Day 1	28.5 ug/mL Geometric Coefficient of Variation 35.3	30.5 ug/mL Geometric Coefficient of Variation 43.1

SECONDARY outcome

Timeframe: EOI on day 1 of cycle 1, 2, and 4

Population: All treated participants with available serum time-concentration data

Serum concentration-time data of nivolumab and ipilimumab administered as a fixed ratio combination to that of sequentially administered nivolumab and ipilimumab is summarized at the end of infusion (EOI). 1 Cycle = 3 weeks

Outcome measures

Measure	Arm A: Fixed Ratio Combination n=52 Participants Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination n=52 Participants Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab Ipilimumab - Cycle 4 Day 1	24.9 ug/mL Geometric Coefficient of Variation 31.3	19.5 ug/mL Geometric Coefficient of Variation 38.5
Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab Ipilimumab - Cycle 1 Day 1	17.6 ug/mL Geometric Coefficient of Variation 23.7	13.4 ug/mL Geometric Coefficient of Variation 61.1
Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab Ipilimumab - Cycle 2 Day 1	21.4 ug/mL Geometric Coefficient of Variation 24.8	15.6 ug/mL Geometric Coefficient of Variation 37.9
Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab Nivolumab - Cycle 1 Day 1	57.1 ug/mL Geometric Coefficient of Variation 22.4	60.7 ug/mL Geometric Coefficient of Variation 23.0
Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab Nivolumab - Cycle 2 Day 1	70.6 ug/mL Geometric Coefficient of Variation 27.6	79.5 ug/mL Geometric Coefficient of Variation 71.9
Geometric Mean End of Infusion (EOI) Concentrations of Nivolumab and Ipilimumab Nivolumab - Cycle 4 Day 1	85.1 ug/mL Geometric Coefficient of Variation 30.1	88.9 ug/mL Geometric Coefficient of Variation 55.1

Adverse Events

Arm A: Fixed Ratio Combination

Serious events: 27 serious events

Other events: 49 other events

Deaths: 26 deaths

Arm B: Sequential Combination

Serious events: 25 serious events

Other events: 48 other events

Deaths: 29 deaths

Serious adverse events

Measure	Arm A: Fixed Ratio Combination n=52 participants at risk Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination n=52 participants at risk Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
Infections and infestations Sepsis	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Cardiac disorders Acute coronary syndrome	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Cardiac disorders Acute myocardial infarction	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Cardiac disorders Atrial fibrillation	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Cardiac disorders Cardiac arrest	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Cardiac disorders Cardiomegaly	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Cardiac disorders Coronary artery disease	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Cardiac disorders Myocardial infarction	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Cardiac disorders Myocardial ischaemia	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Cardiac disorders Myocarditis	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Cardiac disorders Tachycardia	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Endocrine disorders Adrenocortical insufficiency acute	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Urinary tract infection	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Endocrine disorders Hyperthyroidism	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Endocrine disorders Hypophysitis	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Abdominal pain	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Abdominal pain upper	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Colitis	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Diarrhoea	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Enteritis	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Gastrointestinal haemorrhage	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Haematemesis	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Intestinal obstruction	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
General disorders Pyrexia	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Hepatobiliary disorders Autoimmune hepatitis	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Hepatobiliary disorders Biliary obstruction	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Hepatobiliary disorders Drug-induced liver injury	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Achromobacter infection	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations COVID-19	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Gastroenteritis	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Herpes zoster	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Lower respiratory tract infection	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Pneumonia bacterial	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Respiratory tract infection viral	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Urosepsis	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Injury, poisoning and procedural complications Contusion	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Metabolism and nutrition disorders Dehydration	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Metabolism and nutrition disorders Hypercalcaemia	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Metabolism and nutrition disorders Hyperglycaemia	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Metabolism and nutrition disorders Hyperglycaemic hyperosmolar nonketotic syndrome	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Metabolism and nutrition disorders Hypomagnesaemia	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Keratoacanthoma	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Nervous system disorders Cerebrovascular accident	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Nervous system disorders Haemorrhage intracranial	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Nervous system disorders Peripheral sensorimotor neuropathy	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Nervous system disorders Syncope	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Renal and urinary disorders Haematuria	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Renal and urinary disorders Pollakiuria	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Renal and urinary disorders Urinary retention	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Respiratory, thoracic and mediastinal disorders Organising pneumonia	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Vascular disorders Embolism	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Vascular disorders Orthostatic hypotension	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)

Other adverse events

Measure	Arm A: Fixed Ratio Combination n=52 participants at risk Participants recieve a fixed ratio combination (BMS-986237) of nivolumab and ipilimumab in a 3:1 ratio (nivolumab 3 mg/kg and ipilimumab1 mg/kg) every 3 weeks for 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.	Arm B: Sequential Combination n=52 participants at risk Nivolumab 3 mg/kg and ipilimumab 1 mg/kg will be administered sequentially every 3 weeks for up to 4 doses. Participants will then receive nivolumab 480 mg flat dose infused over 30 minutes every four weeks.
Blood and lymphatic system disorders Anaemia	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Blood and lymphatic system disorders Eosinophilia	7.7% 4/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Blood and lymphatic system disorders Leukopenia	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Endocrine disorders Adrenal insufficiency	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Endocrine disorders Hyperthyroidism	7.7% 4/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Endocrine disorders Hypophysitis	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	7.7% 4/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Endocrine disorders Hypothyroidism	23.1% 12/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	15.4% 8/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Abdominal pain	13.5% 7/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Constipation	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Diarrhoea	25.0% 13/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	21.2% 11/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Nausea	13.5% 7/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	7.7% 4/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Gastrointestinal disorders Vomiting	13.5% 7/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
General disorders Asthenia	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
General disorders Fatigue	46.2% 24/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	28.8% 15/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
General disorders Oedema peripheral	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
General disorders Pyrexia	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	7.7% 4/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Hepatobiliary disorders Hepatotoxicity	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Immune system disorders Hypersensitivity	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Bronchitis	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Nasopharyngitis	7.7% 4/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Upper respiratory tract infection	15.4% 8/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Infections and infestations Urinary tract infection	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Injury, poisoning and procedural complications Fall	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Injury, poisoning and procedural complications Infusion related reaction	7.7% 4/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Investigations Alanine aminotransferase increased	15.4% 8/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	11.5% 6/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Investigations Amylase increased	21.2% 11/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	17.3% 9/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Investigations Aspartate aminotransferase increased	13.5% 7/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	11.5% 6/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Investigations Blood alkaline phosphatase increased	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Investigations Blood bilirubin increased	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Investigations Blood cholesterol increased	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	7.7% 4/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Investigations Blood creatinine increased	19.2% 10/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	21.2% 11/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Investigations Blood glucose increased	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Investigations Blood sodium decreased	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	7.7% 4/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Investigations Lipase increased	26.9% 14/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	21.2% 11/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Investigations Weight decreased	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Metabolism and nutrition disorders Decreased appetite	11.5% 6/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Metabolism and nutrition disorders Diabetes mellitus	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Metabolism and nutrition disorders Hypercalcaemia	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Metabolism and nutrition disorders Hyperchloraemia	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	0.00% 0/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Metabolism and nutrition disorders Hyperglycaemia	23.1% 12/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Metabolism and nutrition disorders Hyponatraemia	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Musculoskeletal and connective tissue disorders Arthralgia	15.4% 8/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	15.4% 8/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Musculoskeletal and connective tissue disorders Back pain	13.5% 7/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	15.4% 8/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Musculoskeletal and connective tissue disorders Myalgia	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Musculoskeletal and connective tissue disorders Pain in extremity	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Nervous system disorders Headache	13.5% 7/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	11.5% 6/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Nervous system disorders Syncope	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Psychiatric disorders Insomnia	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Renal and urinary disorders Nephropathy toxic	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Respiratory, thoracic and mediastinal disorders Cough	23.1% 12/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	9.6% 5/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	7.7% 4/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Skin and subcutaneous tissue disorders Pruritus	28.8% 15/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	28.8% 15/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Skin and subcutaneous tissue disorders Rash	38.5% 20/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	19.2% 10/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Skin and subcutaneous tissue disorders Rash maculo-papular	1.9% 1/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)
Vascular disorders Hypotension	3.8% 2/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)	5.8% 3/52 • From the date of first dose to 30 days after last dose of study therapy. (up to approximately 48 months) Participants were assessed for All Cause Mortality from their first dose until the study was completed (up to approximately 52 months)

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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
• Publication restrictions are in place

Restriction type: OTHER