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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03470922
Recruitment Status : Active, not recruiting
First Posted : March 20, 2018
Results First Posted : March 29, 2022
Last Update Posted : October 6, 2022
Sponsor:
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
Recruitment Details  
Pre-assignment Details 714 Participants were randomized and received study treatment
Arm/Group Title Arm A: Relatlimab + Nivolumab Arm B: Nivolumab
Hide 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
Arm/Group Title Arm A: Relatlimab + Nivolumab Arm B: Nivolumab Total
Hide 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
Hide 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%
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Arm A: Relatlimab + Nivolumab Arm B: Nivolumab
Hide 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)
Hide 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)
Hide 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)
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Relatlimab + Nivolumab Arm B: Nivolumab
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Relatlimab + Nivolumab Arm B: Nivolumab
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Relatlimab + Nivolumab Arm B: Nivolumab
Hide 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
Hide Description The number of participant deaths in the study.
Time Frame From first dose up to approximately 33 months
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Arm A: Relatlimab + Nivolumab Arm B: Nivolumab
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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%
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
Hide 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%) 
Hide 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
Hide 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
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
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Phone: Please email
EMail: Clinical.Trials@bms.com
Layout table for additonal information
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: October 6, 2022