An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors

A Phase I/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody (BMS-986016) Administered Alone and in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Advanced Solid Tumors

The purpose of the study is to assess the safety, tolerability and effectiveness of experimental medication BMS-986016 administered alone and in combination with nivolumab in patients with solid tumors that have spread and/or cannot be removed by surgery.

The following tumor types are included in this study:

Non-Small Cell Lung Cancer (NSCLC), gastric cancer, hepatocellular carcinoma, renal cell carcinoma, bladder cancer, squamous cell carcinoma of the head and neck, and melanoma, that have NOT previously been treated with immunotherapy. NSCLC and melanoma that HAVE previously been treated with immunotherapy.

Study Overview

• Status: Completed
• Conditions: Neoplasms by Site
• Intervention / Treatment: Biological: Nivolumab; Biological: Relatlimab; Biological: BMS-986213

• Study Type: Interventional
• Enrollment (Actual): 1482
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia, 2060
      • Local Institution - 0029
  • Queensland
    • Brisbane, Queensland, Australia, 4120
      • Local Institution - 0031
    • Southport, Queensland, Australia, 4215
      • Local Institution - 0039
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Local Institution - 0033
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Local Institution - 0032
• Austria
  • Vienna, Austria, 1090
    • Local Institution - 0023
  • Vienna, Austria, 1090
    • Local Institution - 0024
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0049
  • Quebec
    • Québec, Quebec, Canada, G1J 1Z4
      • Local Institution - 0050
• Denmark
  • Copenhagen, Denmark, 2100
    • Local Institution - 0028
  • Herlev, Denmark, 2730
    • Local Institution - 0020
• Finland
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00290
      • Local Institution - 0021
• France
  • Marseille, France, 13385
    • Local Institution - 0038
  • Nantes, France, 44093
    • Local Institution - 0037
  • Pierre-Bénite, France, 69495
    • Local Institution - 0036
  • Toulouse, France, 31059
    • Local Institution - 0026
  • Villejuif, France, 94800
    • Local Institution - 0018
• Germany
  • Essen, Germany, 45122
    • Local Institution - 0007
  • Heilbronn, Germany, 74078
    • Local Institution - 0040
  • Würzburg, Germany, 97080
    • Local Institution - 0041
• Italy
  • Milan, Italy, 20141
    • Local Institution - 0014
  • Naples, Italy, 80131
    • Local Institution - 0013
  • Padova, Italy, 35128
    • Local Institution - 0035
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 4668560
      • Local Institution - 0055
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 0608543
      • Local Institution - 0059
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 4118777
      • Local Institution - 0054
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 1040045
      • Local Institution - 0052
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1066 CX
      • Local Institution - 0025
• Norway
  • Oslo, Norway, 0379
    • Local Institution - 0019
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 0015
  • Málaga, Spain, 29010
    • Local Institution - 0046
  • Pamplona, Spain, 31008
    • Local Institution - 0006
• Switzerland
  • Lausanne, Switzerland, 1011
    • Local Institution - 0017
  • Zurich, Switzerland, 8091
    • Local Institution - 0016
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Local Institution - 0034
  • Greater London
    • London, Greater London, United Kingdom, NW1 2PG
      • Local Institution - 0027
    • London, Greater London, United Kingdom, SW3 6JJ
      • Local Institution - 0022
• United States
  • California
    • La Jolla, California, United States, 92093-0698
      • Local Institution - 0043
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 0053
  • Florida
    • Tampa, Florida, United States, 33612
      • Local Institution - 0058
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Local Institution - 0003
    • Niles, Illinois, United States, 60714
      • Local Institution - 0048
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Local Institution - 0004
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0001
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Local Institution - 0011
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Local Institution - 0051
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Local Institution - 0044
  • New York
    • New York, New York, United States, 10065
      • Local Institution - 0005
  • Oregon
    • Portland, Oregon, United States, 97213
      • Local Institution - 0002
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Local Institution - 0047
    • Pittsburgh, Pennsylvania, United States, 15232-1305
      • Local Institution - 0010
  • Texas
    • Dallas, Texas, United States, 75246
      • Local Institution - 0057
    • Houston, Texas, United States, 77030
      • Local Institution - 0045
  • Washington
    • Seattle, Washington, United States, 98109
      • Local Institution - 0008

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• For Dose escalation: subjects with cervical, ovarian, bladder and colorectal cancer (CRC), head and neck, gastric and hepatocellular cancer naive to immuno-oncology agents; 1st line melanoma and 1st line/2nd line NSCLC; Renal Cell Carcinoma naive to IO; NSCLC progressing while on or after therapy with anti-PD1/anti-PDL-1 and melanoma subjects progressed while-on or after treatment with anti-PD1 or anti-PDL1 with or without anti-CTLA-4.
• For Dose Expansion: all of the above in escalation except for cervical, ovarian, and CRC
• Progressed, or been intolerant to, at least one standard treatment regimen, except for participants in 1st line cohorts.
• ECOG performance status between 0 and 2
• At least 1 lesion with measurable disease at baseline
• Availability of an existing tumor biopsy sample (and consent to allow pre-treatment tumor biopsy)

Exclusion Criteria:

• Primary central nervous system (CNS) tumors or solid tumors with CNS metastases as the only site of active disease
• Autoimmune disease
• Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
• Uncontrolled CNS metastases

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Relatlimab; Relatlimab (BMS-986016) specified dose on specified days	Biological: Relatlimab; Other Names: BMS-986016; Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
Experimental: Relatlimab + Nivolumab; Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days	Biological: Nivolumab; Other Names: BMS-936558; Anti-PD-1 (Anti-Programmed-Death-1); Biological: Relatlimab; Other Names: BMS-986016; Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
Experimental: BMS-986213; Relatlimab (BMS-986016) + Nivolumab (BMS-936558)	Biological: BMS-986213; Relatlimab + Nivolumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events, Deaths and Clinically Relevant Laboratory Abnormalities	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. SAEs is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization; results significant disability; or is a congenital anomaly/birth defect.	From first dose and within 135 days after last dose of study therapy (Up to approximately 82 months)
Part C, D1, D2, E - Disease Control Rate (DCR) Per BICR	Disease Control Rate (DCR) (as per Recists v1.1) is defined as the percentage of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)
Part D1: Number of Participants With Adverse Events in the Broad Scope Standardized MedDRA (SMQ) Anaphylactic Reaction Occurring Within 2 Days of Any Doses of Study Therapy	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.	From first dose and within 2 days of first dose of study therapy
Part C, D1, D2, E - Objective Response Rate Per BICR	ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)
Part C, D1, D2, E - Duration of Response (DOR) Per BICR	DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. Median computed using Kaplan-Meier method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)
Part C, D1, D2, E - Objective Response Rate Per BICR	ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From first dose (Day 1) and up to 97 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part D1 and D2: Overall Survival (OS) at 12 and 24 Months	Overall survival at 1 year, and 2 years is defined as the proportion of participants who are alive at 1 year, and 2 years. Based on Kaplan-Meier Estimates.	At 12 and 24 months after first dose
Part C, D1, D2, E - Disease Control Rate (DCR) Per Investigator	Disease Control Rate (DCR) (as per Recists v1.1) is defined as the percentage of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)
Maximum Observed Concentration (Cmax) of BMS-986016 (Relatlimab)	Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab).	Day 1 of Cycle 1 and 3
Time to Maximum Observed Concentration (Tmax) of BMS-986016 (Relatlimab)	Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab).	Day 1 of Cycle 1 and 3 (Each cycle consist of 28 days).
Area Under the Concentration-time Curve in One Dosing Interval (AUCtau) of BMS-986016 (Relatlimab)	Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab).	Day 1 of Cycle 1 and 3 (Each cycle consist of 28 days).
Part A/A1, B, C, D1, D2 and E: Trough Observed Concentration (Ctrough) of BMS-986016 (Relatlimab)	Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab). Ctrough is defined as the lowest concentration of drug in the blood immediately before the next dose is administered. Ctrough was only assessed for arm Part A/A1, B, C, D1, D2 and E as pre-specified.	Day 1 of Cycle 3 (Each cycle consist of 28 days)
Part A/A1, B, C AUC Accumulation Index AI_AUC of BMS-986016 (Relatlimab)	Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab). AUC Accumulation Index is a pharmacokinetic metric used to quantify how much a drug accumulates in the body after repeated dosing compared to a single dose. It is ratio of AUC Steady State (AUCss) and AUC1. AUCₛₛ is the area under the plasma concentration-time curve during a dosing interval at steady state (after repeated doses). AUC₁ is the area under the curve after a single dose. Only assessed for arm Part A/A1, B, C as pre-specified.	Day 1 of Cycle 3 (Each cycle consist of 28 days)
Number of Participants With Positive Anti Drug Antibodies	Blood samples were collected to assess anti-drug antibodies.	predose, and 4-hour post-dose of relatlimab on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle consist of 28 days)
Part A, A/A1, and B: Number of Participants With Clinically Relevant QT Prolongation	Abnormal electrocardiogram parameter included QT prolongation.	predose, and 4-hour post-dose of relatlimab on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle consist of 28 days)
Part C, D1 and D2: Progression-Free Survival (PFS) Rate Per BICR	Progression Free Survival Rates at 12 months is defined as the proportion of participants who achieve PFS at 12 months. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Up to 12 months
Part C, D1, D2, E - Objective Response Rate Per Investigator	ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)
Part C, D1, D2, E - Duration of Response (DOR) Per Investigator	DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. Median computed using Kaplan-Meier method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)
Part C, D1 and D2: Progression-Free Survival (PFS) Rate Per Investigator	Progression Free Survival Rates up to 12 months is defined as the proportion of participants who achieve PFS up to 12 months. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Up to 12 months
Part A/A1, B, CTotal Body Clearance (CLT) of BMS-986016 (Relatlimab)	Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab). CLT was only assessed for arm Part A/A1, B, C as pre-specified.	Day 1 of Cycle 3 (Each cycle consist of 28 days).

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Nielsen M, Presti M, Sztupinszki Z, Jensen AWP, Draghi A, Chamberlain CA, Schina A, Yde CW, Wojcik J, Szallasi Z, Crowther MD, Svane IM, Donia M. Coexisting Alterations of MHC Class I Antigen Presentation and IFNgamma Signaling Mediate Acquired Resistance of Melanoma to Post-PD-1 Immunotherapy. Cancer Immunol Res. 2022 Oct 4;10(10):1254-1262. doi: 10.1158/2326-6066.CIR-22-0326.
• Ascierto PA, Tang H, Dolfi S, Nyakas M, Marie Svane I, Munoz-Couselo E, Grob JJ, Gomez-Roca CA, Chiarion-Sileni V, Peltola K, Larkin J, Melero I, Callahan M, Dummer R, Djidel P, Warad D, Reusser-Wolf D, Lipson EJ, Garnett-Benson C. Effect of prior and first-line immunotherapy on baseline immune biomarkers and modulation of the tumor microenvironment in response to nivolumab and relatlimab combination therapy in patients with melanoma from RELATIVITY-020. J Immunother Cancer. 2025 Feb 25;13(2):e009773. doi: 10.1136/jitc-2024-009773.
• Ascierto PA, Lipson EJ, Dummer R, Larkin J, Long GV, Sanborn RE, Chiarion-Sileni V, Dreno B, Dalle S, Schadendorf D, Callahan MK, Nyakas M, Atkinson V, Gomez-Roca CA, Yamazaki N, Tawbi HA, Sarkis N, Warad D, Dolfi S, Mitra P, Suryawanshi S, Grob JJ. Nivolumab and Relatlimab in Patients With Advanced Melanoma That Had Progressed on Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy: Results From the Phase I/IIa RELATIVITY-020 Trial. J Clin Oncol. 2023 May 20;41(15):2724-2735. doi: 10.1200/JCO.22.02072. Epub 2023 Feb 13.
• Huuhtanen J, Kasanen H, Peltola K, Lonnberg T, Glumoff V, Bruck O, Dufva O, Peltonen K, Vikkula J, Jokinen E, Ilander M, Lee MH, Makela S, Nyakas M, Li B, Hernberg M, Bono P, Lahdesmaki H, Kreutzman A, Mustjoki S. Single-cell characterization of anti-LAG-3 and anti-PD-1 combination treatment in patients with melanoma. J Clin Invest. 2023 Mar 15;133(6):e164809. doi: 10.1172/JCI164809.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2013
• Primary Completion (Actual): May 22, 2024
• Study Completion (Actual): February 3, 2025

Study Registration Dates

• First Submitted: September 25, 2013
• First Submitted That Met QC Criteria: October 18, 2013
• First Posted (Estimated): October 23, 2013

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; relatlimab
• Other Study ID Numbers: CA224-020; 2023-508067-70 (Registry Identifier: EU Trial Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No