Effectiveness Study of Nivolumab Compared to Placebo in Prevention of Recurrent Melanoma After Complete Resection of Stage IIB/C Melanoma (CheckMate76K)

• ClinicalTrials.gov Identifier: NCT04099251
• Recruitment Status: Active, not recruiting
• First Posted: September 23, 2019
• Results First Posted: July 27, 2023
• Last Update Posted: November 14, 2023
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Melanoma
• Interventions: Biological: Nivolumab; Other: Placebo
• Enrollment: 790

Participant Flow

Recruitment Details
Pre-assignment Details	980 participants were screened, of which 790 participants were randomized (526 nivolumab/264 placebo) into the study and 788 received either the Nivolumab treatment (524 participants) or placebo (264 participants). 30 eligible participants (2 from the Nivolumab treatment arm and 28 from the placebo arm) received open-label Nivolumab treatment during an optional open-label phase.

Arm/Group Title	Nivolumab	Placebo
Arm/Group Description	Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Period Title: Pre-Treatment
Started [1]	526	264
Completed [2]	524	264
Not Completed	2	0
Reason Not Completed
Other reasons	1	0
Participant no longer meets study criteria	1	0
[1] Started=randomized; [2] Completed=treated
Period Title: Blinded Treatment Phase
Started	524	264
Completed	257	158
Not Completed	267	106
Reason Not Completed
Other reasons	16	7
Disease recurrence	26	41
Adverse event unrelated to study drug	11	1
Study drug toxicity	94	7
Participant no longer meets study criteria	1	0
Lost to Follow-up	1	0
Death	6	2
Withdrawal by Subject	18	7
Participant request to discontinue study treatment	29	0
Ongoing treatment	64	39
Maximum clinical benefit	1	2
Period Title: Optional Open-Label Phase Pre-Treatment
Started [1]	2	30
Completed [2]	2	28
Not Completed	0	2
Reason Not Completed
Participant withdrew consent after re-baseline visit	0	2
[1] Started=Number of participants enrolled in the open-label phase Eligible participants received open-label Nivolumab treatment during a follow-up phase.; [2] Completed=received treatment
Period Title: Optional Open-Label Phase Treatment
Started [1]	2	28
Completed	0	3
Not Completed	2	25
Reason Not Completed
Disease progression/recurrence	0	5
Decision by Principal Investigator	0	1
Study drug toxicity	0	2
Ongoing treatment	2	17
[1] Started=received optional open-label treatment

Baseline Characteristics

Arm/Group Title		Nivolumab	Placebo	Total
Arm/Group Description		Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.	Total of all reporting groups
Overall Number of Baseline Participants		526	264	790
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	526 participants	264 participants	790 participants
		59.9 (13.9)	59.3 (13.6)	59.7 (13.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	526 participants	264 participants	790 participants
	Female	204 38.8%	103 39.0%	307 38.9%
	Male	322 61.2%	161 61.0%	483 61.1%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	526 participants	264 participants	790 participants
	Hispanic or Latino	11 2.1%	6 2.3%	17 2.2%
	Not Hispanic or Latino	317 60.3%	140 53.0%	457 57.8%
	Unknown or Not Reported	198 37.6%	118 44.7%	316 40.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	526 participants	264 participants	790 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	1 0.2%	0 0.0%	1 0.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 0.4%	1 0.4%	3 0.4%
	White	515 97.9%	262 99.2%	777 98.4%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	8 1.5%	1 0.4%	9 1.1%

Outcome Measures

1. Primary Outcome

Title	Recurrence Free Survival (RFS)
Description	Recurrence Free Survival (RFS) is defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (whatever the cause), whichever occurs first. For participants who remain alive and whose disease has not recurred or did not die, RFS will be censored on the date of last evaluable disease assessment. For those participants who remained alive and had no recorded post-randomization tumor assessment, RFS will be censored on the day of randomization.
Time Frame	From randomization up to the date of first recurrence, new primary melanoma, or death (whatever the cause), whichever occurs first (up to 32 months)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Nivolumab	Placebo
Arm/Group Description:	Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Overall Number of Participants Analyzed	526	264
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (28.52 to NA)	NA [1]; (21.62 to NA)

[1]

Median and upper limit not calculated due to insufficient number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nivolumab, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.42
	Confidence Interval	(2-Sided) 95%; 0.30 to 0.59
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Distant Metastasis-Free Survival (DMFS)
Description	Investigator-assessed distant metastasis-free survival (DMFS) is defined as the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first. Participants with no baseline disease assessment, no on-study disease assessments and no death, and no distant metastasis and no death will be censored. Participants with no baseline disease assessment and no on-study disease assessments and death are censored on the date of randomization. Participants with no recurrence and no death will be censored on the date of their last evaluable disease assessment.
Time Frame	From randomization up to the date of first distant metastasis or date of death (whatever the cause), whichever occurs first (up to approximately 32 months)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Nivolumab	Placebo
Arm/Group Description:	Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Overall Number of Participants Analyzed	526	264
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (28.52 to NA)	NA [2]; (NA to NA)

[1]

Median and upper limit not calculated due to insufficient number of events.

[2]

Median, lower and upper limit not calculated due to insufficient number of events.

3. Secondary Outcome

Title	Duration of Treatment on Next Line Therapy Per Investigator Assessment
Description	Duration of treatment is an investigator-assessed outcome of next-line therapy (NLT) defined as the time from first dose date of NLT to last dose date of NLT. Participants who did not stop the NLT were censored.
Time Frame	From first dose date of next-line therapy to last dose date of next-line therapy (up to approximately 32 months)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Nivolumab	Placebo
Arm/Group Description:	Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Overall Number of Participants Analyzed	526	264
Median (95% Confidence Interval); Unit of Measure: Months
	4.17; (2.69 to 8.38)	11.14 [1]; (5.85 to NA)

[1]

Upper limit not calculated due to insufficient number of events

4. Secondary Outcome

Title	Progression-Free Survival Through Next-Line Therapy
Description	Progression-free survival through next-line therapy (PFS2) is defined as the time from randomization to recurrence/objective disease progression after the start of the next-line of systemic anti-cancer therapy, or to the start of a second next-line systemic therapy, or to death from any cause, whichever occurs first. Participants who did not receive subsequent systemic anti-cancer therapy who died will be considered as having the event on the date of death. Participants who received subsequent systemic anti-cancer therapy who had a disease progression after the start of therapy will be considered as having the event on the date of disease progression. Participants who died or started second next-line therapy, the date of death or start date of second next-line therapy will be the event date, whichever is earlier. Participants who did not experience disease progression, death, or second next-line therapy will be censored on the last known alive date.
Time Frame	From randomization to recurrence/objective disease progression after the start of the next-line therapy, or to the start of a second next-line systemic therapy, or to death from any cause, whichever occurs first (up to approximately 32 months)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Nivolumab	Placebo
Arm/Group Description:	Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Overall Number of Participants Analyzed	526	264
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Median, lower and upper limit not calculated due to insufficient number of events

5. Secondary Outcome

Title	Number of Participants Experiencing Adverse Events (AEs)
Description	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.
Time Frame	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Nivolumab	Placebo
Arm/Group Description:	Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Overall Number of Participants Analyzed	524	264
Measure Type: Count of Participants; Unit of Measure: Participants
Any Grade	502 95.8%	229 86.7%
Grade 3-4	115 21.9%	32 12.1%

6. Secondary Outcome

Title	Number of Participants Experiencing Adverse Events Leading to Discontinuation
Description	An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Time Frame	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Nivolumab	Placebo
Arm/Group Description:	Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Overall Number of Participants Analyzed	524	264
Measure Type: Count of Participants; Unit of Measure: Participants
	91 17.4%	9 3.4%

7. Secondary Outcome

Title	Number of Participants Experiencing Select Adverse Events
Description	The number of participants experiencing all-cause select adverse events (AEs). An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
Time Frame	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Nivolumab	Placebo
Arm/Group Description:	Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Overall Number of Participants Analyzed	524	264
Measure Type: Count of Participants; Unit of Measure: Participants
Endocrine	116 22.1%	14 5.3%
Gastrointestinal	122 23.3%	41 15.5%
Hepatic	86 16.4%	35 13.3%
Pulmonary	10 1.9%	1 0.4%
Renal	30 5.7%	10 3.8%
Skin	217 41.4%	64 24.2%
Hypersensitivity/Infusion Reactions	33 6.3%	2 0.8%

8. Secondary Outcome

Title	Number of Participants Experiencing Serious Adverse Events (SAEs)
Description	A Serious Adverse Events (SAE) is defined as any untoward or unfavorable medical occurrence in a participants that results in death, is life threatening, or places the participant at immediate risk of death from the event as it occurred, requires or prolongs hospitalization, causes persistent or significant disability or incapacity, results in congenital anomalies or birth defects, and is another condition which investigators judge to represent significant hazards.
Time Frame	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Nivolumab	Placebo
Arm/Group Description:	Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Overall Number of Participants Analyzed	524	264
Measure Type: Count of Participants; Unit of Measure: Participants
	74 14.1%	29 11.0%

9. Secondary Outcome

Title	Number of Participants Experiencing Death
Description	All study participants who died during the blinded phase of the study following treatment.
Time Frame	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Nivolumab	Placebo
Arm/Group Description:	Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Overall Number of Participants Analyzed	524	264
Measure Type: Count of Participants; Unit of Measure: Participants
	14 2.7%	8 3.0%

10. Secondary Outcome

Title	Number of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities in Selected Hematology Parameters
Description	The number of participants experiencing Grade 3 or 4 laboratory abnormalities in the specific pre-determined hematology tests.
Time Frame	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)

Outcome Measure Data

Analysis Population Description

Participants with at least one on-treatment measurement of the corresponding laboratory parameter

Arm/Group Title		Nivolumab	Placebo
Arm/Group Description:		Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Overall Number of Participants Analyzed		512	261
Measure Type: Count of Participants; Unit of Measure: Participants
PLATELET COUNT	Number Analyzed	512 participants	261 participants
		1 0.2%	0 0.0%
LYMPHOCYTES (ABSOLUTE), LOCAL LAB	Number Analyzed	473 participants	238 participants
		5 1.1%	4 1.7%
ABSOLUTE NEUTROPHIL COUNT	Number Analyzed	512 participants	261 participants
		0 0.0%	1 0.4%

11. Secondary Outcome

Title	Number of Participants Experiencing Laboratory Abnormalities in Selected Liver Parameters
Description	The number of participants experiencing laboratory abnormalities in the specific pre-determined liver tests.
Time Frame	From first dose up to 30 days post last dose of the blinded phase (up to 13 months)

Outcome Measure Data

Analysis Population Description

Participants with at least one on-treatment measurement of the corresponding laboratory parameter

Arm/Group Title		Nivolumab	Placebo
Arm/Group Description:		Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
Overall Number of Participants Analyzed		513	261
Measure Type: Count of Participants; Unit of Measure: Participants
ALT OR AST > 3XULN	Number Analyzed	513 participants	261 participants
		29 5.7%	5 1.9%
ALT OR AST > 5XULN	Number Analyzed	513 participants	261 participants
		16 3.1%	2 0.8%
ALT OR AST > 10XULN	Number Analyzed	513 participants	261 participants
		6 1.2%	0 0.0%
ALT OR AST > 20XULN	Number Analyzed	513 participants	261 participants
		2 0.4%	0 0.0%
TOTAL BILIRUBIN > 2XULN	Number Analyzed	513 participants	261 participants
		3 0.6%	5 1.9%
ALP > 1.5XULN	Number Analyzed	512 participants	261 participants
		20 3.9%	1 0.4%

12. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the time between the date of randomization and the date of death. For those without documentation of death, OS will be censored on the last date the participant was known to be alive.
Time Frame	From randomization up to the date of death or the last date the participant was known to be alive

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Participants were assessed for all-cause mortality from their randomization to primary completion, (up to approximately 32 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 32 months)
Adverse Event Reporting Description	The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Arm/Group Title	Nivolumab	Placebo	Open-Label Nivolumab
Arm/Group Description	Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first. Participants began study treatment (Cycle 1) within 3 calendar days of randomization. Subsequent cycles were initiated within ± 3 days of the target visit date.	Nivolumab matched placebo (0.9% Sodium Chloride for Injection/5% Dextrose for Injection) IV in a 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, withdrawal of consent, completion of 12 months of treatment (from first dose of study treatment), disease recurrence, or the study ends, whichever occurred first.	In the event of disease recurrence, participants on the blinded nivolumab or placebo portion will be offered the option to receive open-label on-protocol nivolumab treatment. Participants received 480 mg IV Nivolumab in an approximately 30-minute infusion on Day 1 of each 4-week treatment cycle until unacceptable toxicity, recurrence/progression, withdrawal of consent, completion of 12 months of treatment from first dose of open-label study treatment, whichever occurred first.
All-Cause Mortality
	Nivolumab	Placebo	Open-Label Nivolumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	14/526 (2.66%)	8/264 (3.03%)	2/32 (6.25%)
Serious Adverse Events
	Nivolumab	Placebo	Open-Label Nivolumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	95/524 (18.13%)	37/264 (14.02%)	5/30 (16.67%)
Blood and lymphatic system disorders
Anaemia † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Thrombocytopenia † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Cardiac disorders
Acute myocardial infarction † 1	2/524 (0.38%)	1/264 (0.38%)	0/30 (0.00%)
Angina unstable † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Cardiac arrest † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Cardiac failure † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Coronary artery disease † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Left ventricular failure † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Myocardial ischaemia † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Myocarditis † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Endocrine disorders
Adrenal insufficiency † 1	3/524 (0.57%)	0/264 (0.00%)	0/30 (0.00%)
Hyperthyroidism † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Hypophysitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Hypopituitarism † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Lymphocytic hypophysitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Eye disorders
Glaucoma † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Uveitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Abdominal pain upper † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Autoimmune colitis † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Autoimmune enteropathy † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Autoimmune pancreatitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Colitis † 1	4/524 (0.76%)	1/264 (0.38%)	1/30 (3.33%)
Diarrhoea † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Enterocolitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Hiatus hernia † 1	0/524 (0.00%)	1/264 (0.38%)	1/30 (3.33%)
Inguinal hernia † 1	1/524 (0.19%)	1/264 (0.38%)	0/30 (0.00%)
Lower gastrointestinal haemorrhage † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Oesophagitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Pancreatitis † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Volvulus † 1	0/524 (0.00%)	0/264 (0.00%)	1/30 (3.33%)
General disorders
General physical health deterioration † 1	0/524 (0.00%)	0/264 (0.00%)	1/30 (3.33%)
Generalised oedema † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Impaired healing † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Malaise † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Pyrexia † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Sudden death † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Hepatobiliary disorders
Autoimmune hepatitis † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Hepatitis † 1	1/524 (0.19%)	1/264 (0.38%)	0/30 (0.00%)
Hepatotoxicity † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Immune system disorders
Contrast media allergy † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Infections and infestations
Abscess limb † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Appendicitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Breast cellulitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Bronchitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
COVID-19 † 1	4/524 (0.76%)	1/264 (0.38%)	0/30 (0.00%)
Cellulitis † 1	1/524 (0.19%)	1/264 (0.38%)	0/30 (0.00%)
Diverticulitis † 1	3/524 (0.57%)	0/264 (0.00%)	0/30 (0.00%)
Erysipelas † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Herpes simplex encephalitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Infected lymphocele † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Infected seroma † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Infective keratitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Osteomyelitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Pneumonia † 1	2/524 (0.38%)	0/264 (0.00%)	1/30 (3.33%)
Sepsis † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Urosepsis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Injury, poisoning and procedural complications
Cervical vertebral fracture † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Fall † 1	1/524 (0.19%)	1/264 (0.38%)	0/30 (0.00%)
Post procedural haematoma † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Subdural haematoma † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Tendon injury † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Upper limb fracture † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Investigations
Alanine aminotransferase increased † 1	4/524 (0.76%)	0/264 (0.00%)	2/30 (6.67%)
Aspartate aminotransferase increased † 1	4/524 (0.76%)	1/264 (0.38%)	1/30 (3.33%)
Hepatic enzyme abnormal † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Hepatic enzyme increased † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Lipase increased † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Troponin increased † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Diabetes mellitus † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Hyperglycaemia † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Hypoglycaemia † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Hyponatraemia † 1	1/524 (0.19%)	1/264 (0.38%)	0/30 (0.00%)
Hypophosphataemia † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Ketoacidosis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Protein deficiency † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Steroid diabetes † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/524 (0.19%)	1/264 (0.38%)	0/30 (0.00%)
Autoimmune myositis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Bone lesion † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Costochondritis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Groin pain † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Immune-mediated myositis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Lumbar spinal stenosis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Muscular weakness † 1	0/524 (0.00%)	0/264 (0.00%)	1/30 (3.33%)
Myositis † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Osteoarthritis † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Osteolysis † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Rhabdomyolysis † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Spondylolisthesis † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	1/524 (0.19%)	1/264 (0.38%)	0/30 (0.00%)
Invasive breast carcinoma † 1	0/524 (0.00%)	2/264 (0.76%)	0/30 (0.00%)
Lentigo maligna † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Malignant melanoma † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Malignant neoplasm progression † 1	1/524 (0.19%)	1/264 (0.38%)	0/30 (0.00%)
Melanoma recurrent † 1	1/524 (0.19%)	2/264 (0.76%)	0/30 (0.00%)
Meningioma † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Metastatic malignant melanoma † 1	2/524 (0.38%)	3/264 (1.14%)	0/30 (0.00%)
Neoplasm malignant † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Vascular neoplasm † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Nervous system disorders
Cerebrovascular disorder † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Dizziness † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Embolic stroke † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Headache † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Polyneuropathy † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Syncope † 1	2/524 (0.38%)	0/264 (0.00%)	0/30 (0.00%)
Transient ischaemic attack † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Psychiatric disorders
Suicidal ideation † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	3/524 (0.57%)	1/264 (0.38%)	1/30 (3.33%)
Chronic kidney disease † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Nephritis † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Nephritis allergic † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Nephrolithiasis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Urinary retention † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Ovarian cyst † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Ovarian hyperstimulation syndrome † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Dyspnoea † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Dyspnoea exertional † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Interstitial lung disease † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Pneumonitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Pneumothorax † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Pulmonary embolism † 1	4/524 (0.76%)	0/264 (0.00%)	0/30 (0.00%)
Pulmonary mass † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Respiratory failure † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Skin and subcutaneous tissue disorders
Urticaria † 1	0/524 (0.00%)	1/264 (0.38%)	1/30 (3.33%)
Vascular disorders
Circulatory collapse † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Deep vein thrombosis † 1	0/524 (0.00%)	1/264 (0.38%)	0/30 (0.00%)
Hypertensive urgency † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Lymphocele † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Peripheral artery aneurysm † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
Vasculitis † 1	1/524 (0.19%)	0/264 (0.00%)	0/30 (0.00%)
1 Term from vocabulary, 25.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Nivolumab	Placebo	Open-Label Nivolumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	464/524 (88.55%)	194/264 (73.48%)	20/30 (66.67%)
Endocrine disorders
Hyperthyroidism † 1	41/524 (7.82%)	4/264 (1.52%)	2/30 (6.67%)
Hypothyroidism † 1	63/524 (12.02%)	0/264 (0.00%)	2/30 (6.67%)
Gastrointestinal disorders
Abdominal pain † 1	22/524 (4.20%)	14/264 (5.30%)	1/30 (3.33%)
Constipation † 1	50/524 (9.54%)	18/264 (6.82%)	3/30 (10.00%)
Diarrhoea † 1	121/524 (23.09%)	44/264 (16.67%)	3/30 (10.00%)
Dry mouth † 1	41/524 (7.82%)	10/264 (3.79%)	4/30 (13.33%)
Eructation † 1	0/524 (0.00%)	0/264 (0.00%)	2/30 (6.67%)
Nausea † 1	78/524 (14.89%)	30/264 (11.36%)	1/30 (3.33%)
Vomiting † 1	19/524 (3.63%)	12/264 (4.55%)	2/30 (6.67%)
General disorders
Asthenia † 1	63/524 (12.02%)	25/264 (9.47%)	4/30 (13.33%)
Fatigue † 1	140/524 (26.72%)	67/264 (25.38%)	6/30 (20.00%)
Pain † 1	11/524 (2.10%)	5/264 (1.89%)	2/30 (6.67%)
Pyrexia † 1	35/524 (6.68%)	13/264 (4.92%)	4/30 (13.33%)
Infections and infestations
COVID-19 † 1	46/524 (8.78%)	23/264 (8.71%)	4/30 (13.33%)
Nasopharyngitis † 1	15/524 (2.86%)	7/264 (2.65%)	2/30 (6.67%)
Injury, poisoning and procedural complications
Infusion related reaction † 1	28/524 (5.34%)	2/264 (0.76%)	0/30 (0.00%)
Investigations
Alanine aminotransferase increased † 1	49/524 (9.35%)	18/264 (6.82%)	3/30 (10.00%)
Aspartate aminotransferase increased † 1	42/524 (8.02%)	7/264 (2.65%)	3/30 (10.00%)
Blood bilirubin increased † 1	16/524 (3.05%)	7/264 (2.65%)	2/30 (6.67%)
Blood creatine phosphokinase increased † 1	55/524 (10.50%)	32/264 (12.12%)	1/30 (3.33%)
Lipase increased † 1	24/524 (4.58%)	9/264 (3.41%)	2/30 (6.67%)
Metabolism and nutrition disorders
Decreased appetite † 1	41/524 (7.82%)	8/264 (3.03%)	2/30 (6.67%)
Hyperglycaemia † 1	28/524 (5.34%)	13/264 (4.92%)	0/30 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	87/524 (16.60%)	31/264 (11.74%)	3/30 (10.00%)
Back pain † 1	28/524 (5.34%)	18/264 (6.82%)	1/30 (3.33%)
Myalgia † 1	41/524 (7.82%)	17/264 (6.44%)	2/30 (6.67%)
Nervous system disorders
Headache † 1	65/524 (12.40%)	34/264 (12.88%)	1/30 (3.33%)
Psychiatric disorders
Confusional state † 1	2/524 (0.38%)	1/264 (0.38%)	2/30 (6.67%)
Insomnia † 1	16/524 (3.05%)	15/264 (5.68%)	0/30 (0.00%)
Renal and urinary disorders
Haematuria † 1	2/524 (0.38%)	3/264 (1.14%)	2/30 (6.67%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	39/524 (7.44%)	12/264 (4.55%)	3/30 (10.00%)
Dyspnoea † 1	28/524 (5.34%)	9/264 (3.41%)	0/30 (0.00%)
Skin and subcutaneous tissue disorders
Pruritus † 1	107/524 (20.42%)	29/264 (10.98%)	3/30 (10.00%)
Rash † 1	69/524 (13.17%)	26/264 (9.85%)	2/30 (6.67%)
Rash maculo-papular † 1	28/524 (5.34%)	6/264 (2.27%)	1/30 (3.33%)
Vascular disorders
Embolism † 1	0/524 (0.00%)	0/264 (0.00%)	2/30 (6.67%)
Hypertension † 1	34/524 (6.49%)	20/264 (7.58%)	0/30 (0.00%)
1 Term from vocabulary, 25.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Results Point of Contact

• Name/Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb
• Phone: Please Email
• EMail: Clinical.Trials@bms.com

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT04099251
• Other Study ID Numbers: CA209-76K; 2019-001230-34 ( EudraCT Number ); U1111-1229-8927 ( Other Identifier: UTN Number )
• First Submitted: September 20, 2019
• First Posted: September 23, 2019
• Results First Submitted: June 26, 2023
• Results First Posted: July 27, 2023
• Last Update Posted: November 14, 2023