A Study of Relatlimab Plus Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma (RELATIVITY-047)

• ClinicalTrials.gov Identifier: NCT03470922
• Recruitment Status: Active, not recruiting
• First Posted: March 20, 2018
• Results First Posted: March 29, 2022
• Last Update Posted: September 21, 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Melanoma
• Interventions: Biological: Relatlimab; Biological: Nivolumab
• Enrollment: 714

Participant Flow

Recruitment Details
Pre-assignment Details	714 Participants were randomized and received study treatment

Arm/Group Title	Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
Arm/Group Description	Participants receive BMS-986213 (IV fixed-dose combination relatlimab/nivolumab at a 1:3 ratio) every 4 weeks (Q4W). For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg.	Participants receive Nivolumab IV monotherapy every 4 weeks (Q4W). Dosing for adults is 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 6 mg/kg.
Period Title: Overall Study
Started	355	359
Completed [1]	237	227
Not Completed	118	132
Reason Not Completed
Death	107	118
Lost to Follow-up	5	5
Participant Withdrew Consent	4	9
Other reasons	1	0
Not reported	1	0
[1] Continuing in the study

Baseline Characteristics

Arm/Group Title		Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab	Total
Arm/Group Description		Participants receive BMS-986213 (IV fixed-dose combination relatlimab/nivolumab at a 1:3 ratio) every 4 weeks (Q4W). For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg.	Participants receive Nivolumab IV monotherapy every 4 weeks (Q4W). Dosing for adults is 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 6 mg/kg.	Total of all reporting groups
Overall Number of Baseline Participants		355	359	714
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	355 participants	359 participants	714 participants
		61.2 (14.1)	61.2 (14.0)	61.2 (14.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	355 participants	359 participants	714 participants
	Female	145 40.8%	153 42.6%	298 41.7%
	Male	210 59.2%	206 57.4%	416 58.3%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	355 participants	359 participants	714 participants
	Hispanic or Latino	27 7.6%	20 5.6%	47 6.6%
	Not Hispanic or Latino	144 40.6%	147 40.9%	291 40.8%
	Unknown or Not Reported	184 51.8%	192 53.5%	376 52.7%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	355 participants	359 participants	714 participants
	American Indian or Alaska Native	0 0.0%	1 0.3%	1 0.1%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	5 1.4%	5 0.7%
	White	342 96.3%	348 96.9%	690 96.6%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	13 3.7%	5 1.4%	18 2.5%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Progression Free Survival (PFS) is defined as the time between the date of randomization and the date of first documented tumor progression, assessed by a blinded independent central review (BICR) (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first. Subjects who die without a reported progression will be considered to have progressed on the date of their death.
Time Frame	From randomization to date of first documented tumor progression or death (up to approximately 33 months)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
Arm/Group Description:	Participants receive BMS-986213 (IV fixed-dose combination relatlimab/nivolumab at a 1:3 ratio) every 4 weeks (Q4W). For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg.	Participants receive Nivolumab IV monotherapy every 4 weeks (Q4W). Dosing for adults is 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 6 mg/kg.
Overall Number of Participants Analyzed	355	359
Median (95% Confidence Interval); Unit of Measure: Months
	10.12; (6.37 to 15.74)	4.63; (3.38 to 5.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Relatlimab + Nivolumab, Arm B: Nivolumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0055
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Log-rank test stratified by LAG-3 (≥ 1% vs < 1%), BRAF (mutation positive vs mutation wild-type), AJCC M-stage (M0/M1any[0] vs M1any[1])
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.62 to 0.92
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. For subjects that are alive, their survival time will be censored at the date of last contact ("last known alive date").
Time Frame	From randomization to the date of death (up to approximately 3 years)

Outcome Measure Data Not Reported

3. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Objective response rate (ORR) is defined as the number of randomized subjects who achieve a best response of complete response (CR) or partial response (PR) based on BICR assessments (using RECIST v1.1 criteria).
Time Frame	From randomization up to approximately 3 years

Outcome Measure Data Not Reported

4. Other Pre-specified Outcome

Title	The Number of Participants Experiencing Adverse Events (AEs)
Description	The number of participants experiencing adverse events (AEs). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time Frame	From first dose to 30 days after last dose of study therapy (up to approximately 33 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
Arm/Group Description:	Participants receive BMS-986213 (IV fixed-dose combination relatlimab/nivolumab at a 1:3 ratio) every 4 weeks (Q4W). For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg.	Participants receive Nivolumab IV monotherapy every 4 weeks (Q4W). Dosing for adults is 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 6 mg/kg.
Overall Number of Participants Analyzed	355	359
Measure Type: Count of Participants; Unit of Measure: Participants
	345 97.2%	339 94.4%

5. Other Pre-specified Outcome

Title	The Number of Participants Experiencing Serious Adverse Events (SAEs)
Description	The number of participants experiencing serious adverse events (SAEs). A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event.
Time Frame	From first dose to 30 days after last dose of study therapy (up to approximately 33 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
Arm/Group Description:	Participants receive BMS-986213 (IV fixed-dose combination relatlimab/nivolumab at a 1:3 ratio) every 4 weeks (Q4W). For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg.	Participants receive Nivolumab IV monotherapy every 4 weeks (Q4W). Dosing for adults is 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 6 mg/kg.
Overall Number of Participants Analyzed	355	359
Measure Type: Count of Participants; Unit of Measure: Participants
	121 34.1%	105 29.2%

6. Other Pre-specified Outcome

Title	The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
Description	The number of participants experiencing adverse events (AEs) leading to discontinuation. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time Frame	From first dose to 30 days after last dose of study therapy (up to approximately 33 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
Arm/Group Description:	Participants receive BMS-986213 (IV fixed-dose combination relatlimab/nivolumab at a 1:3 ratio) every 4 weeks (Q4W). For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg.	Participants receive Nivolumab IV monotherapy every 4 weeks (Q4W). Dosing for adults is 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 6 mg/kg.
Overall Number of Participants Analyzed	355	359
Measure Type: Count of Participants; Unit of Measure: Participants
	69 19.4%	41 11.4%

7. Other Pre-specified Outcome

Title	The Number of Participant Deaths in the Study
Description	The number of participant deaths in the study.
Time Frame	From first dose up to approximately 33 months

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
Arm/Group Description:	Participants receive BMS-986213 (IV fixed-dose combination relatlimab/nivolumab at a 1:3 ratio) every 4 weeks (Q4W). For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg.	Participants receive Nivolumab IV monotherapy every 4 weeks (Q4W). Dosing for adults is 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 6 mg/kg.
Overall Number of Participants Analyzed	355	359
Measure Type: Count of Participants; Unit of Measure: Participants
	108 30.4%	119 33.1%

8. Other Pre-specified Outcome

Title	The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests
Description	The number of participants with clinical laboratory test abnormalities in specific liver tests based on US conventional units.
Time Frame	From first dose to 30 days after last dose of study therapy (up to approximately 33 months)

Outcome Measure Data

Analysis Population Description

All treated participants with at least one on-treatment measurement of the corresponding laboratory parameter

Arm/Group Title		Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
Arm/Group Description:		Participants receive BMS-986213 (IV fixed-dose combination relatlimab/nivolumab at a 1:3 ratio) every 4 weeks (Q4W). For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg.	Participants receive Nivolumab IV monotherapy every 4 weeks (Q4W). Dosing for adults is 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 6 mg/kg.
Overall Number of Participants Analyzed		342	345
Measure Type: Count of Participants; Unit of Measure: Participants
ALT OR AST > 3XULN	Number Analyzed	342 participants	345 participants
		26 7.6%	15 4.3%
ALT OR AST> 5XULN	Number Analyzed	342 participants	345 participants
		11 3.2%	7 2.0%
ALT OR AST> 10XULN	Number Analyzed	342 participants	345 participants
		4 1.2%	4 1.2%
ALT OR AST > 20XULN	Number Analyzed	342 participants	345 participants
		0 0.0%	2 0.6%
TOTAL BILIRUBIN > 2XULN	Number Analyzed	342 participants	345 participants
		2 0.6%	5 1.4%
ALP > 1.5xULN	Number Analyzed	339 participants	345 participants
		34 10.0%	30 8.7%
ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>1.5XULN IN 1 DAY	Number Analyzed	342 participants	345 participants
		2 0.6%	2 0.6%
ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>1.5XULN IN 30 DAYS	Number Analyzed	342 participants	345 participants
		2 0.6%	2 0.6%
ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY	Number Analyzed	342 participants	345 participants
		2 0.6%	1 0.3%
ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS	Number Analyzed	342 participants	345 participants
		2 0.6%	1 0.3%

9. Other Pre-specified Outcome

Title	The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests
Description	The number of participants with clinical laboratory test abnormalities in specific thyroid tests based on US conventional units.
Time Frame	From first dose to 30 days after last dose of study therapy (up to approximately 33 months)

Outcome Measure Data

Analysis Population Description

All treated participants with at least one on-treatment measurement of the corresponding laboratory parameter.

Arm/Group Title		Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
Arm/Group Description:		Participants receive BMS-986213 (IV fixed-dose combination relatlimab/nivolumab at a 1:3 ratio) every 4 weeks (Q4W). For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg.	Participants receive Nivolumab IV monotherapy every 4 weeks (Q4W). Dosing for adults is 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 6 mg/kg.
Overall Number of Participants Analyzed		328	333
Measure Type: Count of Participants; Unit of Measure: Participants
TSH > ULN	Number Analyzed	328 participants	333 participants
		106 32.3%	106 31.8%
TSH > ULN WITH TSH <= ULN AT BASELINE	Number Analyzed	327 participants	331 participants
		84 25.7%	82 24.8%
TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN	Number Analyzed	318 participants	322 participants
		63 19.8%	48 14.9%
TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN	Number Analyzed	318 participants	322 participants
		7 2.2%	7 2.2%
TSH > ULN WITH FT3/FT4 TEST MISSING	Number Analyzed	318 participants	322 participants
		8 2.5%	9 2.8%
TSH < LLN	Number Analyzed	328 participants	333 participants
		89 27.1%	84 25.2%
TSH <LLN WITH TSH >= LLN AT BASELINE	Number Analyzed	327 participants	331 participants
		79 24.2%	78 23.6%
TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN	Number Analyzed	318 participants	322 participants
		51 16.0%	40 12.4%
TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN	Number Analyzed	318 participants	322 participants
		6 1.9%	3 0.9%
TSH < LLN WITH FT3/FT4 TEST MISSING	Number Analyzed	318 participants	322 participants
		11 3.5%	7 2.2%

Adverse Events

Time Frame	From first dose to up to 100 days post last dose (up to approximately 33 months)
Adverse Event Reporting Description	There was a participant in each arm that discontinued the study for reasons unrelated to death but whose deaths records were later discovered in a public search after discontinuation so were included in the All-cause mortality totals.
Arm/Group Title	Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
Arm/Group Description	Participants receive BMS-986213 (IV fixed-dose combination relatlimab/nivolumab at a 1:3 ratio) every 4 weeks (Q4W). For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg.	Participants receive Nivolumab IV monotherapy every 4 weeks (Q4W). Dosing for adults is 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 6 mg/kg.
All-Cause Mortality
	Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	108/355 (30.42%)	119/359 (33.15%)
Serious Adverse Events
	Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	155/355 (43.66%)	140/359 (39.00%)
Blood and lymphatic system disorders
Acquired haemophilia † 1	0/355 (0.00%)	1/359 (0.28%)
Anaemia † 1	5/355 (1.41%)	4/359 (1.11%)
Bone marrow failure † 1	1/355 (0.28%)	0/359 (0.00%)
Haemolytic anaemia † 1	1/355 (0.28%)	0/359 (0.00%)
Cardiac disorders
Acute myocardial infarction † 1	4/355 (1.13%)	2/359 (0.56%)
Arrhythmia † 1	1/355 (0.28%)	0/359 (0.00%)
Atrial fibrillation † 1	1/355 (0.28%)	1/359 (0.28%)
Bradycardia † 1	1/355 (0.28%)	0/359 (0.00%)
Cardiac disorder † 1	1/355 (0.28%)	0/359 (0.00%)
Cardiac failure † 1	0/355 (0.00%)	1/359 (0.28%)
Cardiac failure congestive † 1	0/355 (0.00%)	1/359 (0.28%)
Cardiogenic shock † 1	0/355 (0.00%)	1/359 (0.28%)
Coronary artery disease † 1	0/355 (0.00%)	1/359 (0.28%)
Heart valve incompetence † 1	0/355 (0.00%)	1/359 (0.28%)
Immune-mediated myocarditis † 1	1/355 (0.28%)	0/359 (0.00%)
Myocardial infarction † 1	1/355 (0.28%)	1/359 (0.28%)
Myocardial ischaemia † 1	0/355 (0.00%)	2/359 (0.56%)
Myocarditis † 1	4/355 (1.13%)	1/359 (0.28%)
Palpitations † 1	1/355 (0.28%)	0/359 (0.00%)
Right ventricular dysfunction † 1	0/355 (0.00%)	1/359 (0.28%)
Sinus tachycardia † 1	0/355 (0.00%)	1/359 (0.28%)
Ventricular extrasystoles † 1	2/355 (0.56%)	0/359 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	1/355 (0.28%)	0/359 (0.00%)
Endocrine disorders
Adrenal insufficiency † 1	5/355 (1.41%)	0/359 (0.00%)
Adrenocortical insufficiency acute † 1	1/355 (0.28%)	0/359 (0.00%)
Adrenocorticotropic hormone deficiency † 1	1/355 (0.28%)	0/359 (0.00%)
Autoimmune thyroiditis † 1	1/355 (0.28%)	0/359 (0.00%)
Hyperthyroidism † 1	0/355 (0.00%)	1/359 (0.28%)
Hypophysitis † 1	1/355 (0.28%)	1/359 (0.28%)
Hypothyroidism † 1	1/355 (0.28%)	0/359 (0.00%)
Lymphocytic hypophysitis † 1	1/355 (0.28%)	0/359 (0.00%)
Eye disorders
Autoimmune uveitis † 1	0/355 (0.00%)	1/359 (0.28%)
Papilloedema † 1	0/355 (0.00%)	1/359 (0.28%)
Ulcerative keratitis † 1	1/355 (0.28%)	0/359 (0.00%)
Vision blurred † 1	0/355 (0.00%)	1/359 (0.28%)
Vogt-Koyanagi-Harada disease † 1	1/355 (0.28%)	0/359 (0.00%)
Gastrointestinal disorders
Abdominal distension † 1	1/355 (0.28%)	0/359 (0.00%)
Abdominal pain † 1	3/355 (0.85%)	0/359 (0.00%)
Abdominal pain upper † 1	0/355 (0.00%)	1/359 (0.28%)
Ascites † 1	0/355 (0.00%)	1/359 (0.28%)
Autoimmune colitis † 1	1/355 (0.28%)	1/359 (0.28%)
Colitis † 1	5/355 (1.41%)	1/359 (0.28%)
Constipation † 1	3/355 (0.85%)	0/359 (0.00%)
Diarrhoea † 1	4/355 (1.13%)	3/359 (0.84%)
Gastric volvulus † 1	1/355 (0.28%)	0/359 (0.00%)
Gastritis † 1	2/355 (0.56%)	1/359 (0.28%)
Haemoperitoneum † 1	0/355 (0.00%)	1/359 (0.28%)
Inguinal hernia † 1	0/355 (0.00%)	1/359 (0.28%)
Intestinal obstruction † 1	1/355 (0.28%)	1/359 (0.28%)
Melaena † 1	1/355 (0.28%)	0/359 (0.00%)
Nausea † 1	2/355 (0.56%)	0/359 (0.00%)
Oesophagitis † 1	1/355 (0.28%)	0/359 (0.00%)
Pancreatitis † 1	0/355 (0.00%)	1/359 (0.28%)
Proctalgia † 1	0/355 (0.00%)	1/359 (0.28%)
Rectal haemorrhage † 1	1/355 (0.28%)	1/359 (0.28%)
Small intestinal obstruction † 1	1/355 (0.28%)	0/359 (0.00%)
Upper gastrointestinal haemorrhage † 1	0/355 (0.00%)	3/359 (0.84%)
Vomiting † 1	3/355 (0.85%)	1/359 (0.28%)
General disorders
Asthenia † 1	1/355 (0.28%)	1/359 (0.28%)
Chest pain † 1	0/355 (0.00%)	1/359 (0.28%)
Death † 1	3/355 (0.85%)	1/359 (0.28%)
Disease progression † 1	0/355 (0.00%)	1/359 (0.28%)
Fatigue † 1	1/355 (0.28%)	1/359 (0.28%)
General physical health deterioration † 1	2/355 (0.56%)	6/359 (1.67%)
Inflammation † 1	0/355 (0.00%)	1/359 (0.28%)
Non-cardiac chest pain † 1	1/355 (0.28%)	0/359 (0.00%)
Oedema peripheral † 1	0/355 (0.00%)	1/359 (0.28%)
Pain † 1	0/355 (0.00%)	2/359 (0.56%)
Pyrexia † 1	3/355 (0.85%)	5/359 (1.39%)
Sudden death † 1	0/355 (0.00%)	2/359 (0.56%)
Vascular stent stenosis † 1	1/355 (0.28%)	0/359 (0.00%)
Hepatobiliary disorders
Autoimmune hepatitis † 1	1/355 (0.28%)	0/359 (0.00%)
Bile duct stone † 1	1/355 (0.28%)	0/359 (0.00%)
Cholecystitis † 1	0/355 (0.00%)	1/359 (0.28%)
Cholestasis † 1	0/355 (0.00%)	1/359 (0.28%)
Hepatitis † 1	2/355 (0.56%)	0/359 (0.00%)
Hepatitis toxic † 1	0/355 (0.00%)	1/359 (0.28%)
Hepatotoxicity † 1	1/355 (0.28%)	0/359 (0.00%)
Immune-mediated cholangitis † 1	1/355 (0.28%)	0/359 (0.00%)
Immune-mediated hepatitis † 1	1/355 (0.28%)	1/359 (0.28%)
Immune system disorders
Haemophagocytic lymphohistiocytosis † 1	1/355 (0.28%)	0/359 (0.00%)
Infusion related hypersensitivity reaction † 1	0/355 (0.00%)	1/359 (0.28%)
Infections and infestations
Abscess soft tissue † 1	1/355 (0.28%)	0/359 (0.00%)
Arthritis infective † 1	1/355 (0.28%)	0/359 (0.00%)
Asymptomatic COVID-19 † 1	0/355 (0.00%)	1/359 (0.28%)
Atypical pneumonia † 1	1/355 (0.28%)	1/359 (0.28%)
Bacteraemia † 1	1/355 (0.28%)	0/359 (0.00%)
Bronchitis † 1	1/355 (0.28%)	0/359 (0.00%)
COVID-19 † 1	3/355 (0.85%)	3/359 (0.84%)
COVID-19 pneumonia † 1	1/355 (0.28%)	1/359 (0.28%)
Cellulitis † 1	1/355 (0.28%)	2/359 (0.56%)
Cytomegalovirus colitis † 1	1/355 (0.28%)	0/359 (0.00%)
Device related infection † 1	1/355 (0.28%)	1/359 (0.28%)
Diverticulitis † 1	2/355 (0.56%)	0/359 (0.00%)
Encephalitis † 1	2/355 (0.56%)	1/359 (0.28%)
Erysipelas † 1	1/355 (0.28%)	2/359 (0.56%)
Febrile infection † 1	1/355 (0.28%)	0/359 (0.00%)
Gastroenteritis † 1	0/355 (0.00%)	1/359 (0.28%)
Infected seroma † 1	0/355 (0.00%)	1/359 (0.28%)
Infection † 1	2/355 (0.56%)	1/359 (0.28%)
Influenza † 1	1/355 (0.28%)	0/359 (0.00%)
Lower respiratory tract infection † 1	0/355 (0.00%)	1/359 (0.28%)
Orchitis † 1	1/355 (0.28%)	0/359 (0.00%)
Pneumonia † 1	5/355 (1.41%)	3/359 (0.84%)
Postoperative wound infection † 1	1/355 (0.28%)	0/359 (0.00%)
Pyelonephritis † 1	0/355 (0.00%)	1/359 (0.28%)
Sepsis † 1	3/355 (0.85%)	2/359 (0.56%)
Septic shock † 1	2/355 (0.56%)	0/359 (0.00%)
Streptococcal sepsis † 1	0/355 (0.00%)	1/359 (0.28%)
Suspected COVID-19 † 1	1/355 (0.28%)	0/359 (0.00%)
Tooth abscess † 1	0/355 (0.00%)	1/359 (0.28%)
Tooth infection † 1	0/355 (0.00%)	1/359 (0.28%)
Upper respiratory tract infection † 1	0/355 (0.00%)	1/359 (0.28%)
Urinary tract infection † 1	3/355 (0.85%)	6/359 (1.67%)
Urosepsis † 1	1/355 (0.28%)	1/359 (0.28%)
Injury, poisoning and procedural complications
Accidental overdose † 1	0/355 (0.00%)	1/359 (0.28%)
Fall † 1	1/355 (0.28%)	2/359 (0.56%)
Hip fracture † 1	1/355 (0.28%)	0/359 (0.00%)
Humerus fracture † 1	0/355 (0.00%)	1/359 (0.28%)
Infusion related reaction † 1	0/355 (0.00%)	2/359 (0.56%)
Jaw fracture † 1	0/355 (0.00%)	1/359 (0.28%)
Lower limb fracture † 1	0/355 (0.00%)	1/359 (0.28%)
Lumbar vertebral fracture † 1	0/355 (0.00%)	1/359 (0.28%)
Post procedural discomfort † 1	0/355 (0.00%)	1/359 (0.28%)
Post procedural haemorrhage † 1	0/355 (0.00%)	1/359 (0.28%)
Postoperative thrombosis † 1	1/355 (0.28%)	0/359 (0.00%)
Spinal cord injury † 1	1/355 (0.28%)	0/359 (0.00%)
Spinal fracture † 1	1/355 (0.28%)	1/359 (0.28%)
Thoracic vertebral fracture † 1	1/355 (0.28%)	0/359 (0.00%)
Investigations
Blood creatine phosphokinase MB increased † 1	0/355 (0.00%)	1/359 (0.28%)
Blood creatinine increased † 1	0/355 (0.00%)	1/359 (0.28%)
Lipase increased † 1	1/355 (0.28%)	0/359 (0.00%)
Liver function test increased † 1	1/355 (0.28%)	0/359 (0.00%)
Respiratory syncytial virus test positive † 1	1/355 (0.28%)	0/359 (0.00%)
Transaminases increased † 1	1/355 (0.28%)	0/359 (0.00%)
Troponin T increased † 1	0/355 (0.00%)	1/359 (0.28%)
Troponin increased † 1	3/355 (0.85%)	2/359 (0.56%)
Metabolism and nutrition disorders
Dehydration † 1	2/355 (0.56%)	1/359 (0.28%)
Diabetic ketoacidosis † 1	0/355 (0.00%)	1/359 (0.28%)
Electrolyte imbalance † 1	1/355 (0.28%)	0/359 (0.00%)
Hyperglycaemia † 1	1/355 (0.28%)	0/359 (0.00%)
Hypoalbuminaemia † 1	1/355 (0.28%)	0/359 (0.00%)
Hypocalcaemia † 1	2/355 (0.56%)	0/359 (0.00%)
Hypochloraemia † 1	1/355 (0.28%)	0/359 (0.00%)
Hypoglycaemia † 1	0/355 (0.00%)	1/359 (0.28%)
Hypokalaemia † 1	2/355 (0.56%)	1/359 (0.28%)
Hyponatraemia † 1	3/355 (0.85%)	3/359 (0.84%)
Metabolic acidosis † 1	1/355 (0.28%)	1/359 (0.28%)
Type 1 diabetes mellitus † 1	1/355 (0.28%)	1/359 (0.28%)
Type 2 diabetes mellitus † 1	0/355 (0.00%)	2/359 (0.56%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	3/355 (0.85%)	0/359 (0.00%)
Arthritis † 1	1/355 (0.28%)	1/359 (0.28%)
Autoimmune arthritis † 1	1/355 (0.28%)	1/359 (0.28%)
Back pain † 1	4/355 (1.13%)	2/359 (0.56%)
Bursitis † 1	1/355 (0.28%)	0/359 (0.00%)
Intervertebral disc protrusion † 1	0/355 (0.00%)	1/359 (0.28%)
Muscular weakness † 1	1/355 (0.28%)	1/359 (0.28%)
Myalgia † 1	3/355 (0.85%)	0/359 (0.00%)
Myositis † 1	1/355 (0.28%)	0/359 (0.00%)
Osteoarthritis † 1	1/355 (0.28%)	0/359 (0.00%)
Osteochondrosis † 1	1/355 (0.28%)	0/359 (0.00%)
Pain in extremity † 1	0/355 (0.00%)	2/359 (0.56%)
Pathological fracture † 1	1/355 (0.28%)	0/359 (0.00%)
Polymyalgia rheumatica † 1	2/355 (0.56%)	0/359 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	2/355 (0.56%)	4/359 (1.11%)
Bowen's disease † 1	0/355 (0.00%)	1/359 (0.28%)
Breast cancer † 1	1/355 (0.28%)	0/359 (0.00%)
Cancer pain † 1	1/355 (0.28%)	0/359 (0.00%)
Clear cell sarcoma of soft tissue † 1	0/355 (0.00%)	1/359 (0.28%)
Infected neoplasm † 1	1/355 (0.28%)	1/359 (0.28%)
Malignant neoplasm progression † 1	39/355 (10.99%)	47/359 (13.09%)
Metastases to adrenals † 1	0/355 (0.00%)	1/359 (0.28%)
Metastases to central nervous system † 1	4/355 (1.13%)	3/359 (0.84%)
Metastases to spine † 1	1/355 (0.28%)	0/359 (0.00%)
Metastasis † 1	0/355 (0.00%)	1/359 (0.28%)
Renal cell carcinoma † 1	1/355 (0.28%)	0/359 (0.00%)
Squamous cell carcinoma † 1	1/355 (0.28%)	3/359 (0.84%)
Transitional cell carcinoma † 1	1/355 (0.28%)	0/359 (0.00%)
Tumour associated fever † 1	1/355 (0.28%)	0/359 (0.00%)
Tumour haemorrhage † 1	1/355 (0.28%)	1/359 (0.28%)
Tumour inflammation † 1	1/355 (0.28%)	0/359 (0.00%)
Tumour pain † 1	1/355 (0.28%)	1/359 (0.28%)
Nervous system disorders
Basilar artery thrombosis † 1	0/355 (0.00%)	1/359 (0.28%)
Brain oedema † 1	0/355 (0.00%)	1/359 (0.28%)
Cerebral ischaemia † 1	1/355 (0.28%)	0/359 (0.00%)
Cerebrovascular accident † 1	0/355 (0.00%)	1/359 (0.28%)
Dysdiadochokinesis † 1	1/355 (0.28%)	0/359 (0.00%)
Epilepsy † 1	0/355 (0.00%)	1/359 (0.28%)
Guillain-Barre syndrome † 1	1/355 (0.28%)	0/359 (0.00%)
Haemorrhagic stroke † 1	1/355 (0.28%)	0/359 (0.00%)
Headache † 1	0/355 (0.00%)	1/359 (0.28%)
Hypoaesthesia † 1	1/355 (0.28%)	0/359 (0.00%)
Limbic encephalitis † 1	0/355 (0.00%)	1/359 (0.28%)
Optic neuritis † 1	1/355 (0.28%)	1/359 (0.28%)
Paraesthesia † 1	1/355 (0.28%)	0/359 (0.00%)
Paraplegia † 1	1/355 (0.28%)	0/359 (0.00%)
Radiculopathy † 1	1/355 (0.28%)	0/359 (0.00%)
Seizure † 1	0/355 (0.00%)	1/359 (0.28%)
Spinal cord compression † 1	1/355 (0.28%)	0/359 (0.00%)
Syncope † 1	2/355 (0.56%)	2/359 (0.56%)
Pregnancy, puerperium and perinatal conditions
Pregnancy † 1	1/355 (0.28%)	0/359 (0.00%)
Psychiatric disorders
Confusional state † 1	1/355 (0.28%)	0/359 (0.00%)
Suicide attempt † 1	1/355 (0.28%)	0/359 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	2/355 (0.56%)	3/359 (0.84%)
Immune-mediated nephritis † 1	1/355 (0.28%)	0/359 (0.00%)
Nephrolithiasis † 1	1/355 (0.28%)	1/359 (0.28%)
Proteinuria † 1	1/355 (0.28%)	0/359 (0.00%)
Renal failure † 1	2/355 (0.56%)	0/359 (0.00%)
Tubulointerstitial nephritis † 1	1/355 (0.28%)	0/359 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/355 (0.28%)	0/359 (0.00%)
Chronic obstructive pulmonary disease † 1	1/355 (0.28%)	1/359 (0.28%)
Dysphonia † 1	0/355 (0.00%)	1/359 (0.28%)
Dyspnoea † 1	3/355 (0.85%)	2/359 (0.56%)
Hypoxia † 1	0/355 (0.00%)	1/359 (0.28%)
Immune-mediated pneumonitis † 1	0/355 (0.00%)	1/359 (0.28%)
Increased bronchial secretion † 1	0/355 (0.00%)	1/359 (0.28%)
Lung disorder † 1	0/355 (0.00%)	1/359 (0.28%)
Organising pneumonia † 1	0/355 (0.00%)	1/359 (0.28%)
Pleural effusion † 1	1/355 (0.28%)	2/359 (0.56%)
Pneumonia aspiration † 1	1/355 (0.28%)	0/359 (0.00%)
Pneumonitis † 1	4/355 (1.13%)	1/359 (0.28%)
Pulmonary embolism † 1	2/355 (0.56%)	0/359 (0.00%)
Pulmonary oedema † 1	1/355 (0.28%)	0/359 (0.00%)
Pulmonary sarcoidosis † 1	0/355 (0.00%)	1/359 (0.28%)
Respiratory failure † 1	2/355 (0.56%)	3/359 (0.84%)
Tachypnoea † 1	0/355 (0.00%)	1/359 (0.28%)
Skin and subcutaneous tissue disorders
Dermatitis † 1	0/355 (0.00%)	1/359 (0.28%)
Dermatitis bullous † 1	0/355 (0.00%)	1/359 (0.28%)
Lichen planus † 1	0/355 (0.00%)	1/359 (0.28%)
Pemphigoid † 1	0/355 (0.00%)	1/359 (0.28%)
Rash † 1	1/355 (0.28%)	1/359 (0.28%)
Rash macular † 1	1/355 (0.28%)	0/359 (0.00%)
Skin ulcer † 1	1/355 (0.28%)	0/359 (0.00%)
Surgical and medical procedures
Tumour excision † 1	1/355 (0.28%)	0/359 (0.00%)
Vascular disorders
Aortic aneurysm † 1	1/355 (0.28%)	0/359 (0.00%)
Aortic thrombosis † 1	1/355 (0.28%)	0/359 (0.00%)
Deep vein thrombosis † 1	0/355 (0.00%)	1/359 (0.28%)
Embolism † 1	2/355 (0.56%)	0/359 (0.00%)
Hypertensive crisis † 1	0/355 (0.00%)	1/359 (0.28%)
Hypovolaemic shock † 1	2/355 (0.56%)	0/359 (0.00%)
Iliac artery stenosis † 1	1/355 (0.28%)	0/359 (0.00%)
Shock † 1	1/355 (0.28%)	0/359 (0.00%)
1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm A: Relatlimab + Nivolumab	Arm B: Nivolumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	314/355 (88.45%)	298/359 (83.01%)
Blood and lymphatic system disorders
Anaemia † 1	50/355 (14.08%)	37/359 (10.31%)
Endocrine disorders
Hyperthyroidism † 1	23/355 (6.48%)	28/359 (7.80%)
Hypothyroidism † 1	58/355 (16.34%)	47/359 (13.09%)
Gastrointestinal disorders
Abdominal pain † 1	31/355 (8.73%)	31/359 (8.64%)
Constipation † 1	39/355 (10.99%)	25/359 (6.96%)
Diarrhoea † 1	82/355 (23.10%)	62/359 (17.27%)
Dry mouth † 1	28/355 (7.89%)	18/359 (5.01%)
Nausea † 1	63/355 (17.75%)	59/359 (16.43%)
Vomiting † 1	33/355 (9.30%)	20/359 (5.57%)
General disorders
Asthenia † 1	48/355 (13.52%)	33/359 (9.19%)
Fatigue † 1	104/355 (29.30%)	74/359 (20.61%)
Influenza like illness † 1	19/355 (5.35%)	14/359 (3.90%)
Oedema peripheral † 1	26/355 (7.32%)	21/359 (5.85%)
Pyrexia † 1	44/355 (12.39%)	33/359 (9.19%)
Infections and infestations
Urinary tract infection † 1	38/355 (10.70%)	29/359 (8.08%)
Injury, poisoning and procedural complications
Infusion related reaction † 1	21/355 (5.92%)	12/359 (3.34%)
Investigations
Alanine aminotransferase increased † 1	36/355 (10.14%)	21/359 (5.85%)
Aspartate aminotransferase increased † 1	35/355 (9.86%)	17/359 (4.74%)
Blood creatinine increased † 1	21/355 (5.92%)	12/359 (3.34%)
Troponin increased † 1	27/355 (7.61%)	18/359 (5.01%)
Weight decreased † 1	27/355 (7.61%)	15/359 (4.18%)
Metabolism and nutrition disorders
Decreased appetite † 1	55/355 (15.49%)	27/359 (7.52%)
Hyperglycaemia † 1	19/355 (5.35%)	24/359 (6.69%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	84/355 (23.66%)	54/359 (15.04%)
Back pain † 1	48/355 (13.52%)	30/359 (8.36%)
Myalgia † 1	34/355 (9.58%)	19/359 (5.29%)
Pain in extremity † 1	28/355 (7.89%)	16/359 (4.46%)
Nervous system disorders
Dizziness † 1	21/355 (5.92%)	24/359 (6.69%)
Headache † 1	64/355 (18.03%)	47/359 (13.09%)
Paraesthesia † 1	18/355 (5.07%)	5/359 (1.39%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	50/355 (14.08%)	38/359 (10.58%)
Dyspnoea † 1	33/355 (9.30%)	22/359 (6.13%)
Skin and subcutaneous tissue disorders
Pruritus † 1	88/355 (24.79%)	62/359 (17.27%)
Rash † 1	62/355 (17.46%)	49/359 (13.65%)
Vitiligo † 1	39/355 (10.99%)	37/359 (10.31%)
Vascular disorders
Hypertension † 1	21/355 (5.92%)	14/359 (3.90%)
1 Term from vocabulary, MedDRA 23.1; † 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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Gutierrez E, Rutkowski P, Gogas HJ, Lao CD, De Menezes JJ, Dalle S, Arance A, Grob JJ, Srivastava S, Abaskharoun M, Hamilton M, Keidel S, Simonsen KL, Sobiesk AM, Li B, Hodi FS, Long GV; RELATIVITY-047 Investigators. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022 Jan 6;386(1):24-34. doi: 10.1056/NEJMoa2109970.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT03470922
• Other Study ID Numbers: CA224-047; 2017-003583-12 ( EudraCT Number )
• First Submitted: March 14, 2018
• First Posted: March 20, 2018
• Results First Submitted: January 25, 2022
• Results First Posted: March 29, 2022
• Last Update Posted: September 21, 2023