Neoplasms by SitePhase 1/2NCT01968109
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 1/2 study testing Relatlimab, Nivolumab and BMS-986213 in people with Neoplasms by Site, run by Bristol-Myers Squibb at 54 sites in 15 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Neoplasms by Site
- What is being tested?
- Relatlimab, Nivolumab and BMS-986213
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,482 participants
- Where
- 54 sitesin 15 countries
- Study dates
- 5 Nov 2013to 3 Feb 2025
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
54 sites in 15 countries.
54 sites in 15 countries
United States17 sites
Local Institution - 0047
Allentown, Pennsylvania, 18103
Local Institution - 0053
Aurora, Colorado, 80045
Local Institution - 0004
Baltimore, Maryland, 21287
Local Institution - 0001
Boston, Massachusetts, 02215
Local Institution - 0003
Chicago, Illinois, 60637
Local Institution - 0057
Dallas, Texas, 75246
Local Institution - 0011
Detroit, Michigan, 48201
Local Institution - 0045
Houston, Texas, 77030
Local Institution - 0043
La Jolla, California, 92093-0698
Local Institution - 0005
New York, New York, 10065
Local Institution - 0048
Niles, Illinois, 60714
Local Institution - 0010
Pittsburgh, Pennsylvania, 15232-1305
Local Institution - 0002
Portland, Oregon, 97213
Local Institution - 0051
Rochester, Minnesota, 55905-0001
Local Institution - 0008
Seattle, Washington, 98109
Local Institution - 0044
St Louis, Missouri, 63110
Local Institution - 0058
Tampa, Florida, 33612
Australia5 sites
Local Institution - 0031
Brisbane, Queensland, 4120
Local Institution - 0033
Melbourne, Victoria, 3000
Local Institution - 0032
Nedlands, Western Australia, 6009
Local Institution - 0029
North Sydney, New South Wales, 2060
Local Institution - 0039
Southport, Queensland, 4215
France5 sites
Local Institution - 0038
Marseille, 13385
Local Institution - 0037
Nantes, 44093
Local Institution - 0036
Pierre-Bénite, 69495
Local Institution - 0026
Toulouse, 31059
Local Institution - 0018
Villejuif, 94800
Japan4 sites
Local Institution - 0052
Chuo-ku, Tokyo, 1040045
Local Institution - 0055
Nagoya, Aichi-ken, 4668560
Local Institution - 0059
Sapporo, Hokkaido, 0608543
Local Institution - 0054
Sunto-gun, Shizuoka, 4118777
Germany3 sites
Local Institution - 0007
Essen, 45122
Local Institution - 0040
Heilbronn, 74078
Local Institution - 0041
Würzburg, 97080
Italy3 sites
Local Institution - 0014
Milan, 20141
Local Institution - 0013
Naples, 80131
Local Institution - 0035
Padova, 35128
Spain3 sites
Local Institution - 0015
Barcelona, 08035
Local Institution - 0046
Málaga, 29010
Local Institution - 0006
Pamplona, 31008
United Kingdom3 sites
Local Institution - 0027
London, Greater London, NW1 2PG
Local Institution - 0022
London, Greater London, SW3 6JJ
Local Institution - 0034
Manchester, M20 4BX
Austria2 sites
Local Institution - 0023
Vienna, 1090
Local Institution - 0024
Vienna, 1090
Canada2 sites
Local Institution - 0050
Québec, Quebec, G1J 1Z4
Local Institution - 0049
Toronto, Ontario, M5G 2M9
Denmark2 sites
Local Institution - 0028
Copenhagen, 2100
Local Institution - 0020
Herlev, 2730
Switzerland2 sites
Local Institution - 0017
Lausanne, 1011
Local Institution - 0016
Zurich, 8091
Netherlands1 site
Local Institution - 0025
Amsterdam, North Holland, 1066 CX
About this study
Official title: 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.
- Conditions
- Neoplasms by Site
- Being tested
- Relatlimab, Nivolumab, BMS-986213
- Medical subject headings
- Neoplasms by Site
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RelatlimabBiological
Also called BMS-986016, Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
NivolumabBiological
Also called Anti-PD-1 (Anti-Programmed-Death-1), BMS-936558
BMS-986213Biological
Relatlimab + Nivolumab
| Study group | Role | What they receive |
|---|---|---|
| Relatlimab | Experimental | Relatlimab (BMS-986016) specified dose on specified days Receives: Biological: Relatlimab |
| Relatlimab + Nivolumab | Experimental | Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days Receives: Biological: Relatlimab; Biological: Nivolumab |
| BMS-986213 | Experimental | Relatlimab (BMS-986016) + Nivolumab (BMS-936558) Receives: Biological: BMS-986213 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From first dose (Day 1) and up to 97 months
Secondary outcomes (14)
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.
Measured: Up to 12 months
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.
Measured: At 12 and 24 months after first dose
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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: Up to 12 months
Number of Participants With Positive Anti Drug Antibodies
Blood samples were collected to assess anti-drug antibodies.
Measured: 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.
Measured: predose, and 4-hour post-dose of relatlimab on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle consist of 28 days)
Maximum Observed Concentration (Cmax) of BMS-986016 (Relatlimab)
Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: Day 1 of Cycle 3 (Each cycle consist of 28 days)
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.
Measured: 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.
Measured: Day 1 of Cycle 3 (Each cycle consist of 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2013 (estimated)
- Study start5 Nov 2013
- Primary completion22 May 2024
- Study completion3 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Neoplasms by SiteStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,482 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01968109
- Sponsor's protocol ID
- CA224-020
- Other IDs
- 2023-508067-70, 2023
- Status last verified
- Mar 2026
- First submitted
- 25 Sep 2013
- Last updated
- 6 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40010775Ascierto 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.
PubMed 36780608Huuhtanen 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.
PubMed 36719749Nielsen 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.
PubMed 35969233