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

NCT01968109 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: CA224-0202023-508067-70
• Study Type: interventional
• Target: 1,482
• Locations: 14 countries
• Sites: 52

Brief Summary

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.

Conditions

Neoplasms by Site

Outcome Measures

Primary Outcomes (6)

• 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 - 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 - 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 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 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 (Day 1) and up to 97 months

Secondary Outcomes (14)

• Part C, D1 and D2: Progression-Free Survival (PFS) Rate up to 12 Months Per BICR

  Up to 12 months

• Part D1 and D2: Overall Survival (OS) at 12 and 24 Months

  At 12 and 24 months after first dose

• Part C, D1, D2, E - Objective Response Rate Per Investigator

  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 - Disease Control Rate (DCR) Per Investigator

  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

  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)

Study Arms (3)

Relatlimab

EXPERIMENTAL

Relatlimab (BMS-986016) specified dose on specified days

Biological: Relatlimab

Relatlimab + Nivolumab

EXPERIMENTAL

Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days

Biological: Relatlimab; Biological: Nivolumab

BMS-986213

EXPERIMENTAL

Relatlimab (BMS-986016) + Nivolumab (BMS-936558)

Biological: BMS-986213

Interventions

Relatlimab BIOLOGICAL

Also known as: BMS-986016, Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)

Relatlimab; Relatlimab + Nivolumab

Nivolumab BIOLOGICAL

Also known as: Anti-PD-1 (Anti-Programmed-Death-1), BMS-936558

Relatlimab + Nivolumab

BMS-986213 BIOLOGICAL

Relatlimab + Nivolumab

BMS-986213

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (54)

Local Institution - 0043

La Jolla, California, 92093-0698, United States

Location

Local Institution - 0053

Aurora, Colorado, 80045, United States

Location

Local Institution - 0058

Tampa, Florida, 33612, United States

Location

Local Institution - 0003

Chicago, Illinois, 60637, United States

Location

Local Institution - 0048

Niles, Illinois, 60714, United States

Location

Local Institution - 0004

Baltimore, Maryland, 21287, United States

Location

Local Institution - 0001

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0011

Detroit, Michigan, 48201, United States

Location

Local Institution - 0051

Rochester, Minnesota, 55905-0001, United States

Location

Local Institution - 0044

St Louis, Missouri, 63110, United States

Location

Local Institution - 0005

New York, New York, 10065, United States

Location

Local Institution - 0002

Portland, Oregon, 97213, United States

Location

Local Institution - 0047

Allentown, Pennsylvania, 18103, United States

Location

Local Institution - 0010

Pittsburgh, Pennsylvania, 15232-1305, United States

Location

Local Institution - 0057

Dallas, Texas, 75246, United States

Location

Local Institution - 0045

Houston, Texas, 77030, United States

Location

Local Institution - 0008

Seattle, Washington, 98109, United States

Location

Local Institution - 0029

North Sydney, New South Wales, 2060, Australia

Location

Local Institution - 0031

Brisbane, Queensland, 4120, Australia

Location

Local Institution - 0039

Southport, Queensland, 4215, Australia

Location

Local Institution - 0033

Melbourne, Victoria, 3000, Australia

Location

Local Institution - 0032

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0023

Vienna, 1090, Austria

Location

Local Institution - 0024

Vienna, 1090, Austria

Location

Local Institution - 0049

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 0050

Québec, Quebec, G1J 1Z4, Canada

Location

Local Institution - 0028

Copenhagen, 2100, Denmark

Location

Local Institution - 0020

Herlev, 2730, Denmark

Location

Local Institution - 0021

Helsinki, Uusimaa, 00290, Finland

Location

Local Institution - 0038

Marseille, 13385, France

Location

Local Institution - 0037

Nantes, 44093, France

Location

Local Institution - 0036

Pierre-Bénite, 69495, France

Location

Local Institution - 0026

Toulouse, 31059, France

Location

Local Institution - 0018

Villejuif, 94800, France

Location

Local Institution - 0007

Essen, 45122, Germany

Location

Local Institution - 0040

Heilbronn, 74078, Germany

Location

Local Institution - 0041

Würzburg, 97080, Germany

Location

Local Institution - 0014

Milan, 20141, Italy

Location

Local Institution - 0013

Naples, 80131, Italy

Location

Local Institution - 0035

Padua, 35128, Italy

Location

Local Institution - 0055

Nagoya, Aichi-ken, 4668560, Japan

Location

Local Institution - 0059

Sapporo, Hokkaido, 0608543, Japan

Location

Local Institution - 0054

Sunto-gun, Shizuoka, 4118777, Japan

Location

Local Institution - 0052

Chuo-ku, Tokyo, 1040045, Japan

Location

Local Institution - 0025

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Local Institution - 0019

Oslo, 0379, Norway

Location

Local Institution - 0015

Barcelona, 08035, Spain

Location

Local Institution - 0046

Málaga, 29010, Spain

Location

Local Institution - 0006

Pamplona, 31008, Spain

Location

Local Institution - 0017

Lausanne, 1011, Switzerland

Location

Local Institution - 0016

Zurich, 8091, Switzerland

Location

Local Institution - 0027

London, Greater London, NW1 2PG, United Kingdom

Location

Local Institution - 0022

London, Greater London, SW3 6JJ, United Kingdom

Location

Local Institution - 0034

Manchester, M20 4BX, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 40010775 DERIVED

• 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.

  PMID: 36780608 DERIVED

• 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.

  PMID: 36719749 DERIVED

• 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.

  PMID: 35969233 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Neoplasms by Site

Interventions

relatlimab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2013
• First Posted: October 23, 2013
• Study Start: November 5, 2013
• Primary Completion: May 22, 2024
• Study Completion: February 3, 2025
• Last Updated: January 6, 2026
• Results First Posted: January 6, 2026

Record last verified: 2025-12

Locations

DE (3); AU (5); ES (3); NO (1); DK (2); CA (2); IT (3); JP (4); FI (1); NL (1); US (17); CH (2); GB (3); FR (5)