Trial Outcomes & Findings for A Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Melanoma (NCT NCT02905266)

NCT ID: NCT02905266

Last Updated: 2020-12-17

Results Overview

This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction broad scope SMQ. Such AEs include any acute systemic reaction characterized by a large list of terms, including (but not limited to) pruritus, urticaria, flushing, hypotension, respiratory distress, and vascular insufficiency. It also includes other signs and symptoms such as asthma, choking sensation, coughing, sneezing, and difficulty breathing due to laryngeal spasm and/or bronchospasm. Less frequent clinical presentations are also captured and include hyperventilation, sensation of foreign body, and ocular edema.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 106 participants
• Primary outcome timeframe: Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
• Results posted on: 2020-12-17

Participant Flow

106 participants were randomized and treated.

Participant milestones

Measure	Fixed Ratio Combination Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Treatment Phase Part 1 STARTED	53	53
Treatment Phase Part 1 COMPLETED	24	30
Treatment Phase Part 1 NOT COMPLETED	29	23
Transition From Part 1 to Part 2 STARTED	24	30
Transition From Part 1 to Part 2 COMPLETED	20	22
Transition From Part 1 to Part 2 NOT COMPLETED	4	8
Maintenance Phase Part 2 STARTED	20	22
Maintenance Phase Part 2 COMPLETED	8	14
Maintenance Phase Part 2 NOT COMPLETED	12	8

Reasons for withdrawal

Measure	Fixed Ratio Combination Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Treatment Phase Part 1 Participant Withdrew Consent	1	0
Treatment Phase Part 1 Disease Progression	6	7
Treatment Phase Part 1 Study Drug Toxicity	22	16
Transition From Part 1 to Part 2 Adverse event unrelated to study drug	1	0
Transition From Part 1 to Part 2 Disease progression	2	1
Transition From Part 1 to Part 2 Study drug toxicity	0	4
Transition From Part 1 to Part 2 Death	0	1
Transition From Part 1 to Part 2 Participant withdrew consent	0	1
Transition From Part 1 to Part 2 Adverse Event	1	1
Maintenance Phase Part 2 Disease Progression	9	2
Maintenance Phase Part 2 Study Drug Toxicity	3	4
Maintenance Phase Part 2 Maximum Clinical Benefit	0	2

Baseline Characteristics

A Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Melanoma

Baseline characteristics by cohort

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Total n=106 Participants Total of all reporting groups
Age, Continuous	58.1 years STANDARD_DEVIATION 14.5 • n=5 Participants	56.3 years STANDARD_DEVIATION 14.6 • n=7 Participants	57.2 years STANDARD_DEVIATION 14.5 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	26 Participants n=7 Participants	44 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	27 Participants n=7 Participants	62 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	28 Participants n=7 Participants	54 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	26 Participants n=5 Participants	24 Participants n=7 Participants	50 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	48 Participants n=5 Participants	50 Participants n=7 Participants	98 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)

Population: All treated participants

This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction broad scope SMQ. Such AEs include any acute systemic reaction characterized by a large list of terms, including (but not limited to) pruritus, urticaria, flushing, hypotension, respiratory distress, and vascular insufficiency. It also includes other signs and symptoms such as asthma, choking sensation, coughing, sneezing, and difficulty breathing due to laryngeal spasm and/or bronchospasm. Less frequent clinical presentations are also captured and include hyperventilation, sensation of foreign body, and ocular edema.

Outcome measures

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Percentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ)	15.1 Percent of Participants Interval 6.7 to 27.6	17.0 Percent of Participants Interval 8.1 to 29.8

SECONDARY outcome

Timeframe: Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)

Population: All treated participants

This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction narrow scope SMQ. The narrow scope SMQ is composed of a large list of terms, including (but not limited to) anaphylactic shock and reaction, shock and shock symptoms, and circulatory collapse, among the others.

Outcome measures

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Percentage of Participants Affected by AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ	0.0 Percent of Participants Interval 0.0 to 6.7	0.0 Percent of Participants Interval 0.0 to 6.7

SECONDARY outcome

Timeframe: Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)

Population: All treated participants

This outcome describes the percentage of participants experiencing at least 1 AE in the Hypersensitivity/Infusion select AEs category. The select AEs consist of a list of preferred terms defined by the Sponsor and represent AEs with a potential immune-mediated etiology. The following 5 MedDRA preferred terms are included in the hypersensitivity/infusion reaction select AE category: Anaphylactic Reaction, Anaphylactic Shock, Bronchospasm, Hypersensitivity, and Infusion Related Reaction

Outcome measures

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Percentage of Participants Affected by Hypersensitivity/Infusion Reaction Select AEs	7.5 Percent of Participants	9.4 Percent of Participants

SECONDARY outcome

Timeframe: From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)

Population: All treated participants

This outcome describes the percentage of participants who experienced at least 1 AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria

Outcome measures

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Percentage of Participants Affected by All Causality Grade 3 - 5 AEs	69.8 Percent of participants	56.6 Percent of participants

SECONDARY outcome

Timeframe: From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)

Population: All treated participants

This outcome describes the percentage of participants who experienced at least 1 Drug-related AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria

Outcome measures

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Percentage of Participants Affected by Drug-related Grade 3 - 5 AEs	58.5 Percent of participants	47.2 Percent of participants

SECONDARY outcome

Timeframe: From Cycle 1, Day 1 to Cycle 4, Day 1 (approximately 9 weeks). Each cycle lasts 3 weeks. Cycle 1 day 1, Cycle 2 day 1 and Cycle 4 day 1 values reported.

Population: All treated participants

Outcome measures

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Geometric Mean Concentration of Ipilimumab at End of Infusion (EOI) Cycle 1 Day 1	60.4 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 93.0	61.5 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 72.3
Geometric Mean Concentration of Ipilimumab at End of Infusion (EOI) Cycle 2 Day 1	66.8 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 134	72.1 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 71.8
Geometric Mean Concentration of Ipilimumab at End of Infusion (EOI) Cycle 4 Day 1	77.9 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 94.2	84.6 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 104

SECONDARY outcome

Timeframe: From Cycle 1, Day 1 to Cycle 4, Day 1 (approximately 9 weeks). Each cycle lasts 3 weeks. Cycle 1 day 1, Cycle 2 day 1 and Cycle 4 day 1 values reported

Population: All treated participants

Outcome measures

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Geometric Mean Concentration of Nivolumab at End of Infusion (EOI) Cycle 1 Day 1	20.9 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 77.3	21.8 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 117
Geometric Mean Concentration of Nivolumab at End of Infusion (EOI) Cycle 2 Day 1	24.2 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 122	22.4 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 101
Geometric Mean Concentration of Nivolumab at End of Infusion (EOI) Cycle 4 Day 1	27.9 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 79.8	27.4 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 79.9

SECONDARY outcome

Timeframe: From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.

Population: All treated participants

Outcome measures

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Geometric Mean Trough Concentration of Ipilimumab Cycle 4 Day 1	16.5 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 36.9	13.7 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 46.0
Geometric Mean Trough Concentration of Ipilimumab Cycle 2 Day 1	10.8 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 30.2	9.94 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 38.9

SECONDARY outcome

Timeframe: From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.

Population: All treated participants

Outcome measures

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Geometric Mean Trough Concentration of Nivolumab Cycle 4 Day 1	6.50 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 44.6	4.05 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 75.3
Geometric Mean Trough Concentration of Nivolumab Cycle 2 Day 1	3.94 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 56.6	2.75 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 65.9

SECONDARY outcome

Timeframe: Week 12 following randomization, every 8 weeks for the first 12 months and then every 12 weeks until disease progression (approximately 20 months)

Population: All treated participants

The ORR is defined as the proportion 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 subsequent anti-cancer therapy, whichever occurs first.

Outcome measures

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Objective Response Rate (ORR)	52.8 Percentage of Participants Interval 38.6 to 66.7	60.4 Percentage of Participants Interval 46.0 to 73.5

SECONDARY outcome

Timeframe: From the date of randomization to the first date of documented progression (approximately 26 months)

Population: All treated participants

PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first.

Outcome measures

Measure	Fixed Ratio Combination n=53 Participants Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 Participants Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Progression Free Survival (PFS)	10.25 Months Interval 2.96 to Upper limit not reached because of insufficient number of participants with an event	NA Months Interval 4.96 to (Value) N.A.explanation: Below the level of detection (Upper limit) n/a explanation: Upper limit not reached because of insufficient number of participants with an event

Adverse Events

Fixed Ratio Combination

Serious events: 35 serious events

Other events: 51 other events

Deaths: 14 deaths

Sequential Combination

Serious events: 35 serious events

Other events: 51 other events

Deaths: 14 deaths

Serious adverse events

Measure	Fixed Ratio Combination n=53 participants at risk Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 participants at risk Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Cardiac disorders Angina pectoris	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Cardiac disorders Atrial fibrillation	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Endocrine disorders Adrenal insufficiency	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Endocrine disorders Hypophysitis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Endocrine disorders Thyroiditis	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Eye disorders Iridocyclitis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Abdominal pain	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Abdominal pain upper	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Ascites	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Autoimmune colitis	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Colitis	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Cyclic vomiting syndrome	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Diarrhoea	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Duodenitis	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Enteritis	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Erosive duodenitis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Gastritis	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Immune-mediated enterocolitis	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Intestinal perforation	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Melaena	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Pancreatitis acute	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Rectal haemorrhage	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Vomiting	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Adverse drug reaction	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Chest pain	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders General physical health deterioration	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Oedema peripheral	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Pyrexia	15.1% 8/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Hepatobiliary disorders Acute hepatic failure	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Hepatobiliary disorders Autoimmune hepatitis	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Hepatobiliary disorders Cholangitis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Hepatobiliary disorders Hepatitis	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Hepatobiliary disorders Hepatocellular injury	11.3% 6/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Hepatobiliary disorders Hypertransaminasaemia	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Immune system disorders Autoimmune disorder	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Immune system disorders Drug hypersensitivity	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Anal abscess	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Bacterial infection	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Erysipelas	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Gastroenteritis viral	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Lower respiratory tract infection	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Meningitis aseptic	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Parotitis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Pneumonia	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Respiratory tract infection	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Urinary tract infection	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Urosepsis	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Alanine aminotransferase increased	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Aspartate aminotransferase increased	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Liver function test abnormal	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Pancreatic enzymes increased	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Pneumocystis test positive	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Transaminases increased	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Dehydration	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Arthralgia	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Haematoma muscle	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip squamous cell carcinoma	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	13.2% 7/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Facial paralysis	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Guillain-Barre syndrome	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Headache	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Meningorrhagia	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Motor neurone disease	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Spinal cord compression	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Dysuria	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Glomerulonephritis rapidly progressive	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Hydronephrosis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Tubulointerstitial nephritis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Urinary tract obstruction	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Reproductive system and breast disorders Ovarian cyst	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Cough	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Dermatitis bullous	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Vascular disorders Thrombosis	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).

Other adverse events

Measure	Fixed Ratio Combination n=53 participants at risk Concomitant administration of Nivolumab and Ipilimumab (1:3 protein-mass ratio) every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase	Sequential Combination n=53 participants at risk Sequential administration of Nivolumab and Ipilimumab every 3 weeks for 4 doses followed by Nivolumab flat dose in the Maintenance Phase
Blood and lymphatic system disorders Anaemia	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	11.3% 6/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Endocrine disorders Hyperthyroidism	15.1% 8/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	11.3% 6/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Endocrine disorders Hypophysitis	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Endocrine disorders Hypothyroidism	20.8% 11/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	15.1% 8/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Endocrine disorders Thyroiditis	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Abdominal distension	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Abdominal pain	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Abdominal pain upper	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Colitis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Constipation	17.0% 9/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	13.2% 7/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Diarrhoea	30.2% 16/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	47.2% 25/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Dry mouth	11.3% 6/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Gastrooesophageal reflux disease	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Nausea	17.0% 9/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	22.6% 12/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Gastrointestinal disorders Vomiting	17.0% 9/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	22.6% 12/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Asthenia	32.1% 17/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	37.7% 20/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Chills	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Fatigue	18.9% 10/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	17.0% 9/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Influenza like illness	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	15.1% 8/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Oedema peripheral	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
General disorders Pyrexia	26.4% 14/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	34.0% 18/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Hepatobiliary disorders Hepatitis	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Hepatobiliary disorders Hepatocellular injury	13.2% 7/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Bronchitis	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Nasopharyngitis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Oral herpes	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Sinusitis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Infections and infestations Urinary tract infection	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Injury, poisoning and procedural complications Infusion related reaction	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Alanine aminotransferase increased	15.1% 8/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	13.2% 7/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Amylase increased	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Aspartate aminotransferase increased	11.3% 6/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Blood lactate dehydrogenase increased	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Gamma-glutamyltransferase increased	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Investigations Lipase increased	15.1% 8/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Decreased appetite	18.9% 10/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	13.2% 7/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Metabolism and nutrition disorders Hypokalaemia	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Arthralgia	18.9% 10/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	18.9% 10/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Back pain	15.1% 8/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	11.3% 6/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Musculoskeletal and connective tissue disorders Myalgia	13.2% 7/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	15.1% 8/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Dizziness	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Headache	15.1% 8/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	28.3% 15/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Nervous system disorders Paraesthesia	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Psychiatric disorders Insomnia	7.5% 4/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Psychiatric disorders Sleep disorder	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Renal and urinary disorders Dysuria	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Cough	24.5% 13/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	13.2% 7/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Erythema	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Hyperhidrosis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Lichenoid keratosis	1.9% 1/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Night sweats	3.8% 2/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Pruritus	17.0% 9/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	32.1% 17/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Rash	28.3% 15/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	22.6% 12/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Rash pruritic	17.0% 9/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	13.2% 7/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Skin and subcutaneous tissue disorders Vitiligo	17.0% 9/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	9.4% 5/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).
Vascular disorders Deep vein thrombosis	5.7% 3/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).	0.00% 0/53 • From first dose to 100 days following administration of the last dose (approximately 27 months).

Additional Information

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Bristol-Myers Squibb

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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.
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Restriction type: OTHER