MelanomaPhase 2NCT03743766
Nivolumab, BMS-936558 in Combination With Relatlimab, BMS-986016 in Patients With Metastatic Melanoma Naïve to Prior Immunotherapy in the Metastatic Setting
A Phase 2 study testing Relatlimab, Nivolumab and Relatlimab + Nivolumab in people with Melanoma, run by John Kirkwood at 1 site in United States.
Trial summary
The main goal of this study is to evaluate the antitumor activity of relatlimab and nivolumab in combination in subjects with unresectable or metastatic melanoma who have not received prior treatment with immunotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Relatlimab, Nivolumab and Relatlimab + Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Mar 2019to 3 Jul 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women 18 years of age or older meeting AJCC 8th edition criteria for unresectable stage IIIB, stage IIIC, stage IIID, or stage IV melanoma who have not received treatment with immunotherapy in the metastatic setting
Who cannot join
- Known or suspected CNS metastases, with the following exceptions:
- Subjects with controlled brain metastases will be allowed to enroll. Controlled brain metastases are defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment at the time of consent. Subjects must be off steroids for at least 2 weeks prior to randomization.
- Subjects with signs or symptoms of brain metastases are not eligible unless brain metastases are ruled out by computed tomography or magnetic resonance imaging.
- Active autoimmune disease requiring treatment, with the exception of type 1 diabetes mellitus, vitiligo, resolved childhood asthma/atopy, controlled hyper/hypothyroidism, hypoadrenalism or hypopituitarism.
- Prior systemic treatment in the metastatic setting, including anti-PD1, anti-PDL1, anti-PDL2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways; or chemotherapy.
- Prior adjuvant treatment with anti-PD1, anti-PDL1, and/or anti-LAG3 antibody. Note that prior adjuvant treatment with targeted therapy (e.g. BRAF/MEK inhibition), anti-CTLA4, or treatment not otherwise specified above would be permitted.
- Ocular melanoma
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Phase II Study of Anti-PD1 Monoclonal Antibody (Nivolumab, BMS-936558) Administered in Combination With Anti-LAG3 Monoclonal Antibody (Relatlimab, BMS-986016) in Patients With Metastatic Melanoma Naïve to Prior Immunotherapy in the Metastatic Setting
The main goal of this study is to evaluate the antitumor activity of relatlimab and nivolumab in combination in subjects with unresectable or metastatic melanoma who have not received prior treatment with immunotherapy.
Read the detailed description
This study will evaluate the antitumor activity of anti-LAG3 monoclonal antibody relatlimab and the anti-PD1 monoclonal antibody nivolumab in combination in subjects with unresectable or metastatic melanoma who have not received prior treatment with immunotherapy. The trial is designed with a lead-in phase of 2 cycles (4 week) treatment of either nivolumab, relatlimab, or the combination of nivolumab/relatlimab, followed by a combination phase of nivolumab/relatlimab treatment in all subjects. This lead-in design with accompanying tumor biopsies and peripheral blood analyses will enable mechanistic analyses of the effect of LAG3 and PD1 blockade alone and in combination to enhance understanding of mechanisms of response and resistance. Duration of response, progression free survival, and safety will be assessed as secondary objectives.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RelatlimabDrug
Also called BMS-986016
Relatlimab (BMS-986016) - 10mg/mL formulation to be administered as an intravenous (IV) infusion at 160 mg IV.
NivolumabDrug
Also called BMS-936558
Nivolumab (BMS-936558) - 10-mg/mL formulation to be administered as an IV infusion at 480 mg IV.
Relatlimab + NivolumabDrug
Also called BMS-986016 and BMS-936558
Combination (Relatlimab + Nivolumab) therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV.
| Study group | Role | What they receive |
|---|---|---|
| Relatlimab | Experimental | Cycle 1: Relatlimab (BMS-986016) is supplied as a sterile 10mg/mL formulation to be administered as an intravenous (IV) infusion at 160 mg IV for the first 4 weeks (cycle 1).
Cycle 2+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV once every 4 weeks. Receives: Drug: Relatlimab |
| Nivolumab | Experimental | Cycle 1: Nivolumab (BMS-936558) is supplied as a sterile 10-mg/mL formulation to be administered as an IV infusion at 480 mg IV for the first 4 weeks.
Cycle 2+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV once every 4 weeks. Receives: Drug: Nivolumab |
| Relatlimab + Nivolumab | Experimental | Cycle 1+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV for the first 4 weeks (Cycle 1), then once every 4 weeks afterwards. Receives: Drug: Relatlimab + Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
LAG3 Gene Expression From scRNAseq
Percent Lymphocyte-activation gene 3 (LAG3) level (cell surface molecule expressed on activated T cells) expression from scRNAseq
Measured: At Baseline
LAG3 Gene Expression From scRNAseq
Percent Lymphocyte-activation gene 3 (LAG3) level (cell surface molecule expressed on activated T cells) expression from scRNAseq
Measured: At Week 4
PD1 Expression
Percent PD1 (programmed cell death protein 1) expression after completion of lead-in phase.
Measured: At baseline (Week 0)
PD1 Expression
Percent PD1 (programmed cell death protein 1) expression after completion of lead-in phase.
Measured: At Week 4
Change in Tumor Size
Percentage change in tumor size assessed per Response Evaluation Criteria in Solid Tumors. Per RECIST 1.1, Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of:
- 10 mm by CT scan (CT scan slice thickness no greater than 5 mm; see Appendix II on imaging guidance).
- 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as non-measurable).
- 20 mm by chest X-ray.
Measured: At baseline and at 4 weeks
Overall Response Rate (ORR)
Percent of participants experiencing Complete Response (CR) + Number of participants experiencing Partial Response (PR)/total patients assessed. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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. (Note: the appearance of one or more new lesions is also considered progression). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: Beginning at 12 weeks post initial treatment, up to 4 years
Overall Response Rate (ORR) - ITT (Intent-to-treat) Population
Percent of participants experiencing Complete Response (CR) + Number of participants experiencing Partial Response (PR)/total patients assessed. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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. (Note: the appearance of one or more new lesions is also considered progression). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: Beginning at 12 weeks post initial treatment, up to 4 years
Secondary outcomes (41)
Secondary Outcome: Clinical Benefit Rate
Percent of patients with Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) / total patients assessed per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: 12 weeks post initial treatment, up to 4 years
Clinical Benefit Rate - ITT (Intent-to-treat) Population
Percent of patients with Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) / total patients assessed per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: 12 weeks post initial treatment, up to 4 years
Duration of Response
Time from first documented Complete Response (CR) or Partial Response (PR) until the first date that progressive disease is objectively documented. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: 12 weeks post initial treatment, up to 4 years
Progression-free Survival (PFS)
Progression-free survival is defined as the time between the date of randomization and the first date of documented progression or death due to any cause, whichever occurs first. Per RECIST v1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 4 years
Progression-free Survival (PFS) by Lead-in Arm
Progression-free survival is defined as the time between the date of randomization and the first date of documented progression or death due to any cause, whichever occurs first. Per RECIST v1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 4 years
Overall Survival (OS)
Overall survival is defined as the time between the date of randomization and the date of death due to any cause.
Measured: Up to 4 years
CD8+ Tumor Infiltrating Lymphocytes
Number of CD8+ tumor infiltrating lymphocytes present.
Measured: At Baseline
CD8+ Tumor Infiltrating Lymphocytes
Number of CD8+ tumor infiltrating lymphocytes present.
Measured: At Week 4
CD4+ Tumor Infiltrating Lymphocytes
Number of CD4+ tumor infiltrating lymphocytes present.
Measured: At Week 4
CD4+ Tumor Infiltrating Lymphocytes
Number of CD4+ tumor infiltrating lymphocytes present.
Measured: At Baseline
LAG3 Levels - PBMC
To determine the amount of LAG3 expressed on activated T cells in the blood through single-cell RNA sequencing. The LAG3 expression is reported as the natural log (ln) of the number of LAG3 transcripts divided by the number of total mapped reads plus 1.
Measured: At Baseline
LAG3 Levels - PBMC
To determine the amount of LAG3 expressed on activated T cells in the blood through single-cell RNA sequencing. The LAG3 expression is reported as the natural log (ln) of the number of LAG3 transcripts divided by the number of total mapped reads plus 1.
Measured: At Week 4
LAG3 Levels - TIL
To determine the amount of LAG3 expressed on activated tumor infiltrating lymphocytes (TIL) through single-cell RNA sequencing. The LAG3 expression is reported as the natural log (ln) of the number of LAG3 transcripts divided by the number of total mapped reads plus 1.
Measured: At Baseline
LAG3 Levels - PBMC
To determine the amount of LAG3 expressed on activated T cells in the blood through single-cell RNA sequencing. The LAG3 expression is reported as the natural log (ln) of the number of LAG3 transcripts divided by the number of total mapped reads plus 1.
Measured: At Week 16
LAG3 Levels - TIL
To determine the amount of LAG3 expressed on activated tumor infiltrating lymphocytes (TIL) through single-cell RNA sequencing. The LAG3 expression is reported as the natural log (ln) of the number of LAG3 transcripts divided by the number of total mapped reads plus 1.
Measured: At Week 4
PD-1 Expression in PBMC
To determine the amount of PD-1 (programmed cell death protein 1) expressed on PBMCs through single-cell RNA sequencing in treated patients. The PD-1 expression is reported as the natural log (ln) of the number of PD-1 transcripts divided by the number of total mapped reads plus 1.
Measured: At Baseline
PD-1 Expression in PBMC
To determine the amount of PD-1 (programmed cell death protein 1) expressed on PBMCs through single-cell RNA sequencing in treated patients. The PD-1 expression is reported as the natural log (ln) of the number of PD-1 transcripts divided by the number of total mapped reads plus 1.
Measured: At Week 4
PD-1 Expression in PBMC
To determine the amount of PD-1 (programmed cell death protein 1) expressed on PBMCs through single-cell RNA sequencing in treated patients. The PD-1 expression is reported as the natural log (ln) of the number of PD-1 transcripts divided by the number of total mapped reads plus 1.
Measured: At Week 16
PD-1 Expression in TIL
To determine the amount of PD-1 (programmed cell death protein 1) expressed on TILs through single-cell RNA sequencing in treated patients. The PD-1 expression is reported as the natural log (ln) of the number of PD-1 transcripts divided by the number of total mapped reads plus 1.
Measured: At Baseline
PD-1 Expression in TIL
To determine the amount of PD-1 (programmed cell death protein 1) expressed on TILs through single-cell RNA sequencing in treated patients. The PD-1 expression is reported as the natural log (ln) of the number of PD-1 transcripts divided by the number of total mapped reads plus 1.
Measured: At Week 4
Cell Effector/Memory Status - TIL
Measure of cells that have previously encountered and responded to their cognate antigen in TIL.
Measured: At Baseline
Cell Effector/Memory Status - TIL
Measure of cells that have previously encountered and responded to their cognate antigen in TIL.
Measured: At Week 4
Cell Effector/Memory Status - PBMCs
Measure of cells that have previously encountered and responded to their cognate antigen in PBMCs.
Measured: At Baseline
Cell Effector/Memory Status - PBMC
Measure of cells that have previously encountered and responded to their cognate antigen in PBMCs.
Measured: At Week 4
Cell Effector/Memory Status - PBMC
Measure of cells that have previously encountered and responded to their cognate antigen in PBMCs.
Measured: At Week 16
Regulatory T Cell (Treg) Marker Levels - PMBCs
Amount of Regulatory T cell (Treg) markers present in PBMCs in treated patients.
Measured: At Baseline
Regulatory T Cell (Treg) Marker Levels - PMBCs
Amount of Regulatory T cell (Treg) markers present in PBMCs in treated patients.
Measured: At Week 4
Regulatory T Cell (Treg) Marker Levels - PMBCs
Amount of Regulatory T cell (Treg) markers present in PBMCs in treated patients.
Measured: At Week 16
Regulatory T Cell (Treg) Marker Levels - TIL
Amount of Regulatory T cell (Treg) markers present in TILs in treated patients.
Measured: At Baseline
Regulatory T Cell (Treg) Marker Levels - TIL
Amount of Regulatory T cell (Treg) markers present in TILs in treated patients.
Measured: At Week 4
Activation and Maturation of Dendritic Cells - PBMC
Measure of expression of activation and maturation of dendritic cells in PBMCs.
Measured: At Baseline
Activation and Maturation of Dendritic Cells - PBMC
Measure of expression of activation and maturation of dendritic cells in PBMCs.
Measured: At Week 4
Activation and Maturation of Dendritic Cells - PBMC
Measure of expression of activation and maturation of dendritic cells in PBMCs.
Measured: At Week 16
Activation and Maturation of Dendritic Cells - TIL
Measure of expression of activation and maturation of dendritic cells in tumor (TIL).
Measured: At Baseline
Activation and Maturation of Dendritic Cells - TIL
Measure of expression of activation and maturation of dendritic cells in tumor (TIL).
Measured: At Week 4
Soluble LAG3 Levels - PBMC
Amount of LAG3 (cell surface molecule expressed on activated T cells) protein present in blood in patients that had previously demonstrated complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: At the time of disease progression - up to 4 years
Soluble LAG3 Levels - TIL
Amount of LAG3 (cell surface molecule expressed on activated T cells) protein present in tumor tissue in patients that had previously demonstrated complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: At the time of disease progression - up to 4 years
Granzyme B Serum Levels
Level of granzyme B (a serine protease secreted cells to mediate apoptosis in target cells) in serum.
Measured: At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks
T Cell Count
Number of T cells present in TIL or PBMC.
Measured: At 4 weeks
T Cell Count
Number of T cells present in TIL or PBMC.
Measured: At 12 weeks
T Cell Count
Number of T cells present in TIL or PBMC.
Measured: At the time of disease progression - up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2018
- Study start29 Mar 2019
- Primary completion3 Jul 2024
- Study completion3 Jul 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.
- Other trials for MelanomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In the 4-week lead-in phase, subjects will be randomized to one of three arms for 1 cycle (4 weeks) of lead-in treatment with nivolumab, relatlimab, or the combination of nivolumab and relatlimab. Following 1 cycle of lead-in treatment, all subjects will be treated with the combination of relatlimab and nivolumab every 4 weeks.
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- John Kirkwood
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, John Kirkwood, University of Pittsburgh
- Investigators
- John Kirkwood, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03743766
- Sponsor's protocol ID
- 18-071
- Status last verified
- Dec 2025
- First submitted
- 18 Oct 2018
- Last updated
- 31 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Anti-PD1 Monoclonal Antibody (Nivolumab, BMS-936558) Administered in Combination With Anti-LAG3 Monoclonal Antibody (Relatlimab, BMS-986016) in Patients With Metastatic Melanoma Naïve to Prior Immunotherapy in the Metastatic Setting
- ClinicalTrials.gov ID
- NCT03743766
- Acronym / sponsor ID
- 18-071
- Conditions
- Melanoma
- Keywords
- Stage IIIB, Stage IIIC, Stage IIID, Stage IV, immune checkpoint blockade (ICB), Lymphocyte activation gene-3 (LAG3; CD223), immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- John KirkwoodUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 29 Mar 2019 (actual)
- Primary completion
- 3 Jul 2024 (actual)
- Study completion
- 3 Jul 2025 (actual)
- First posted
- 16 Nov 2018 (actual)
- Results
- Posted 31 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main goal of this study is to evaluate the antitumor activity of relatlimab and nivolumab in combination in subjects with unresectable or metastatic melanoma who have not received prior treatment with immunotherapy.
Detailed description
This study will evaluate the antitumor activity of anti-LAG3 monoclonal antibody relatlimab and the anti-PD1 monoclonal antibody nivolumab in combination in subjects with unresectable or metastatic melanoma who have not received prior treatment with immunotherapy. The trial is designed with a lead-in phase of 2 cycles (4 week) treatment of either nivolumab, relatlimab, or the combination of nivolumab/relatlimab, followed by a combination phase of nivolumab/relatlimab treatment in all subjects. This lead-in design with accompanying tumor biopsies and peripheral blood analyses will enable mechanistic analyses of the effect of LAG3 and PD1 blockade alone and in combination to enhance understanding of mechanisms of response and resistance. Duration of response, progression free survival, and safety will be assessed as secondary objectives.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- In the 4-week lead-in phase, subjects will be randomized to one of three arms for 1 cycle (4 weeks) of lead-in treatment with nivolumab, relatlimab, or the combination of nivolumab and relatlimab. Following 1 cycle of lead-in treatment, all subjects will be treated with the combination of relatlimab and nivolumab every 4 weeks.
| Arm | Type | Receives |
|---|---|---|
| Relatlimab | Experimental | Drug: RelatlimabCycle 1: Relatlimab (BMS-986016) is supplied as a sterile 10mg/mL formulation to be administered as an intravenous (IV) infusion at 160 mg IV for the first 4 weeks (cycle 1). Cycle 2+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV once every 4 weeks. |
| Nivolumab | Experimental | Drug: NivolumabCycle 1: Nivolumab (BMS-936558) is supplied as a sterile 10-mg/mL formulation to be administered as an IV infusion at 480 mg IV for the first 4 weeks. Cycle 2+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV once every 4 weeks. |
| Relatlimab + Nivolumab | Experimental | Drug: Relatlimab + NivolumabCycle 1+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV for the first 4 weeks (Cycle 1), then once every 4 weeks afterwards. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Men or women 18 years of age or older meeting AJCC 8th edition criteria for unresectable stage IIIB, stage IIIC, stage IIID, or stage IV melanoma who have not received treatment with immunotherapy in the metastatic setting
Key exclusion criteria (7 listed)
- Known or suspected CNS metastases, with the following exceptions:
- Active autoimmune disease requiring treatment, with the exception of type 1 diabetes mellitus, vitiligo, resolved childhood asthma/atopy, controlled hyper/hypothyroidism, hypoadrenalism or hypopituitarism.
- Prior systemic treatment in the metastatic setting, including anti-PD1, anti-PDL1, anti-PDL2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways; or chemotherapy.
- Prior adjuvant treatment with anti-PD1, anti-PDL1, and/or anti-LAG3 antibody. Note that prior adjuvant treatment with targeted therapy (e.g. BRAF/MEK inhibition), anti-CTLA4, or treatment not otherwise specified above would be permitted.
- Ocular melanoma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RelatlimabAlso: BMS-986016Relatlimab (BMS-986016) - 10mg/mL formulation to be administered as an intravenous (IV) infusion at 160 mg IV. | Drug | Relatlimab |
| NivolumabAlso: BMS-936558Nivolumab (BMS-936558) - 10-mg/mL formulation to be administered as an IV infusion at 480 mg IV. | Drug | Nivolumab |
| Relatlimab + NivolumabAlso: BMS-986016 and BMS-936558Combination (Relatlimab + Nivolumab) therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV. | Drug | Relatlimab + Nivolumab |
Primary outcome
LAG3 Gene Expression From scRNAseq
Time frame: At Baseline
Percent Lymphocyte-activation gene 3 (LAG3) level (cell surface molecule expressed on activated T cells) expression from scRNAseq
LAG3 Gene Expression From scRNAseq
Time frame: At Week 4
Percent Lymphocyte-activation gene 3 (LAG3) level (cell surface molecule expressed on activated T cells) expression from scRNAseq
PD1 Expression
Time frame: At baseline (Week 0)
Percent PD1 (programmed cell death protein 1) expression after completion of lead-in phase.
PD1 Expression
Time frame: At Week 4
Percent PD1 (programmed cell death protein 1) expression after completion of lead-in phase.
Change in Tumor Size
Time frame: At baseline and at 4 weeks
Percentage change in tumor size assessed per Response Evaluation Criteria in Solid Tumors. Per RECIST 1.1, Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of: * 10 mm by CT scan (CT scan slice thickness no greater than 5 mm; see Appendix II on imaging guidance). * 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as non-measurable). * 20 mm by chest X-ray.
Overall Response Rate (ORR)
Time frame: Beginning at 12 weeks post initial treatment, up to 4 years
Percent of participants experiencing Complete Response (CR) + Number of participants experiencing Partial Response (PR)/total patients assessed. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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. (Note: the appearance of one or more new lesions is also considered progression). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Overall Response Rate (ORR) - ITT (Intent-to-treat) Population
Time frame: Beginning at 12 weeks post initial treatment, up to 4 years
Percent of participants experiencing Complete Response (CR) + Number of participants experiencing Partial Response (PR)/total patients assessed. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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. (Note: the appearance of one or more new lesions is also considered progression). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
41 secondary outcomes
Secondary Outcome: Clinical Benefit Rate
Time frame: 12 weeks post initial treatment, up to 4 years
Clinical Benefit Rate - ITT (Intent-to-treat) Population
Time frame: 12 weeks post initial treatment, up to 4 years
Duration of Response
Time frame: 12 weeks post initial treatment, up to 4 years
Progression-free Survival (PFS)
Time frame: Up to 4 years
Progression-free Survival (PFS) by Lead-in Arm
Time frame: Up to 4 years
Overall Survival (OS)
Time frame: Up to 4 years
CD8+ Tumor Infiltrating Lymphocytes
Time frame: At Baseline
CD8+ Tumor Infiltrating Lymphocytes
Time frame: At Week 4
CD4+ Tumor Infiltrating Lymphocytes
Time frame: At Week 4
CD4+ Tumor Infiltrating Lymphocytes
Time frame: At Baseline
LAG3 Levels - PBMC
Time frame: At Baseline
LAG3 Levels - PBMC
Time frame: At Week 4
LAG3 Levels - TIL
Time frame: At Baseline
LAG3 Levels - PBMC
Time frame: At Week 16
LAG3 Levels - TIL
Time frame: At Week 4
PD-1 Expression in PBMC
Time frame: At Baseline
PD-1 Expression in PBMC
Time frame: At Week 4
PD-1 Expression in PBMC
Time frame: At Week 16
PD-1 Expression in TIL
Time frame: At Baseline
PD-1 Expression in TIL
Time frame: At Week 4
Cell Effector/Memory Status - TIL
Time frame: At Baseline
Cell Effector/Memory Status - TIL
Time frame: At Week 4
Cell Effector/Memory Status - PBMCs
Time frame: At Baseline
Cell Effector/Memory Status - PBMC
Time frame: At Week 4
Cell Effector/Memory Status - PBMC
Time frame: At Week 16
Regulatory T Cell (Treg) Marker Levels - PMBCs
Time frame: At Baseline
Regulatory T Cell (Treg) Marker Levels - PMBCs
Time frame: At Week 4
Regulatory T Cell (Treg) Marker Levels - PMBCs
Time frame: At Week 16
Regulatory T Cell (Treg) Marker Levels - TIL
Time frame: At Baseline
Regulatory T Cell (Treg) Marker Levels - TIL
Time frame: At Week 4
Activation and Maturation of Dendritic Cells - PBMC
Time frame: At Baseline
Activation and Maturation of Dendritic Cells - PBMC
Time frame: At Week 4
Activation and Maturation of Dendritic Cells - PBMC
Time frame: At Week 16
Activation and Maturation of Dendritic Cells - TIL
Time frame: At Baseline
Activation and Maturation of Dendritic Cells - TIL
Time frame: At Week 4
Soluble LAG3 Levels - PBMC
Time frame: At the time of disease progression - up to 4 years
Soluble LAG3 Levels - TIL
Time frame: At the time of disease progression - up to 4 years
Granzyme B Serum Levels
Time frame: At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks
T Cell Count
Time frame: At 4 weeks
T Cell Count
Time frame: At 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Kirkwood, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Relatlimab, Nivolumab and Relatlimab + Nivolumab in people with Melanoma, run by John Kirkwood at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LAG3 Gene Expression From scRNAseq (time frame: At Baseline). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.