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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Relatlimab | Drug | Relatlimab (BMS-986016) - 10mg/mL formulation to be administered as an intravenous (IV) infusion at 160 mg IV. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in LAG3 Expression | LAG3 (cell surface molecule expressed on activated T cells) expression is either positive (present) or not detectable if absent after completion of lead-in phase. | At baseline and at 4 weeks |
| Change in PD1 expression | PD1 (programmed cell death protein 1) expression is either positive (present) or not detectable if absent after completion of lead-in phase | At baseline and at 4 weeks |
| Change in Tumor Size | Tumor size will be assessed per Response Evaluation Criteria in Solid Tumors. Per RECIST 1.1, Tumour 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:
| At baseline and at 4 weeks |
| Overall Response Rate (ORR) | Number 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Benefit Rate | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Single cell RNA sequencing | The presence and quantity of RNA in in blood and tumor tissue. | 2 weeks |
| Single cell RNA sequencing | The presence and quantity of RNA in in blood and tumor tissue. |
Inclusion Criteria:
• 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
Exclusion Criteria:
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
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| Name | Affiliation | Role |
|---|---|---|
| John Kirkwood, MD | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania | 15232 | United States |
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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.
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| Nivolumab | Drug | Nivolumab (BMS-936558) - 10-mg/mL formulation to be administered as an IV infusion at 480 mg IV. |
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| Relatlimab + Nivolumab | Drug | 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. |
|
|
| Beginning at 12 weeks post initial treatment, up to 4 years |
| 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. | 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. | 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. | Up to 4 years |
| LAG3 Expression | LAG3 (cell surface molecule expressed on activated T cells) expression (positive (present) or not detectable if absent) in tumor and peripheral blood of treated participants who experience a complete response, partial response, or stable disease, prior to ultimately experiencing disease progression. | At week 16 (2 weeks post combination treatment (3 cycles)) |
| PD-1 Expression | PD-1 (programmed cell death protein 1) expression (positive (present) or not detectable if absent) in tumor and peripheral blood of treated participants who experience a complete response, partial response, or stable disease, prior to ultimately experiencing disease progression. | At week 16 (12 weeks post combination treatment (3 cycles)) |
| Change in CD4+ tumor infiltrating lymphocytes | Percentage and number of CD4+ tumor infiltrating lymphocytes present | At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks |
| Change in CD8+ tumor infiltrating lymphocytes | Percentage and number of CD8+ tumor infiltrating lymphocytes present | At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks |
| Change in granzyme B serum levels | Level of granzyme B (a serine protease secreted cells to mediate apoptosis in target cells) in serum. | At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks |
| Change in cell effector/memory status | Measure of cells that have previously encountered and responded to their cognate antigen. | At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks |
| Change in activation and maturation of dendritic cells | Measure of expression of activation and maturation of dendritic cells | At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks |
| Change in T cell count | Number of T cells present in blood and tumor | At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks |
| Change in T cell count | Number of T cells present in blood and tumor 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. | At the time of disease progression - up to 4 years |
| Change in soluble LAG3 levels | Amount of LAG3 (cell surface molecule expressed on activated T cells) protein present in blood and tumor tissue. | At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks |
| Soluble LAG3 levels | Amount of LAG3 (cell surface molecule expressed on activated T cells) protein present in blood and 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. | At the time of disease progression - up to 4 years |
| Change in Regulatory T cell (Treg) marker level | Amount of Regulatory T cell (Treg) markers present in blood and tumor tissue. | At 2 weeks prior first study treatment, at 4 weeks, at 12 weeks |
| Regulatory T cell (Treg) marker levels | Amount of Regulatory T cell (Treg) markers present in blood and 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. | At the time of disease progression - up to 4 years |
| At 4 weeks post Cycle 1 |
| Single cell RNA sequencing | The presence and quantity of RNA in in blood and tumor tissue. | At week 16 (12 weeks post combination treatment (3 cycles) |
| Single cell RNA sequencing | The presence and quantity of RNA in in blood and 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. | At the time of disease progression - up to 4 years |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jul 3, 2025 | Jul 21, 2025 | 11 | ||
| Dec 7, 2025 | Dec 23, 2025 | 12 | ||
| May 17, 2026 | Jun 11, 2026 | 13 |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C000721227 | relatlimab |
| D000077594 | Nivolumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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