A Study of Subcutaneous Nivolumab + Relatlimab Fixed-dose Combination (FDC) in Previously Untreated Metastatic or Unresectable Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that the study drug exposure level of the nivolumab + relatlimab FDC subcutaneous (SC) formulation is not worse than nivolumab + relatlimab FDC intravenous (IV) administration in participants with previously untreated metastatic or unresectable melanoma.

Official Title
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A Phase 3, Randomized, Open-label, Study of Subcutaneous Nivolumab + Relatlimab Fixed-dose Combination Versus Intravenous Nivolumab + Relatlimab Fixed-dose Combination in Participants With Previously Untreated Metastatic or Unresectable Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Nivolumab + Relatlimab
* Drug: rHuPH20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1/Lansky Performance Score ≥ 80% for adolescents (≥ 12 to < 18 years of age). Participants must have histologically confirmed Stage III (unresectable) or Stage IV (metastatic) melanoma, per the American Joint Committee for Cancer (AJCC) staging system. Participants must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Participants must be ≥ 12 years of age. Participants who are ≥ 12 years of age and < 18 years of age (adolescents) must weigh ≥ 40 kg at the time of signing the informed consent (assent). Participants must have histologically confirmed Stage III (unresectable) or Stage IV (metastatic) melanoma, per the AJCC staging system (8th edition). Exclusion Criteria: Participants must not have ocular melanoma. Participants must not have a history of myocarditis, regardless of etiology. Participants must not have a condition requiring systemic treatment with either corticosteroids (>10 milligrams [mg] daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab + Relatlimab FDC SC<br> | Drug: Nivolumab + Relatlimab<br>* Specified dose on specified days<br>* Other names: Opdualag;Drug: rHuPH20<br>* Specified dose on specified days<br>|
| Active Comparator: Nivolumab + Relatlimab FDC IV<br> | Drug: Nivolumab + Relatlimab<br>* Specified dose on specified days<br>* Other names: Opdualag;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-averaged serum concentration over 28 days after the first dose (Cavgd28) of Nivolumab |  | Up to 28 days | 
| Trough serum concentration at steady state (Cminss) of Nivolumab |  | Up to 4 months | 
| Cavgd28 of Relatlimab |  | Up to 28 days | 
| Cminss of Relatlimab |  | Up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) per RECIST v1.1 |  | Up to approximately 3 years | 
| Trough serum concentration at Day 28 after the first dose (Cmind28) of Nivolumab and Relatlimab |  | Up to 28 days | 
| Peak serum concentration after the first dose (Cmax1) of Nivolumab and Relatlimab |  | Up to 28 days | 
| Time to Cmax1 (Tmax1) of Nivolumab and Relatlimab |  | Up to 28 days | 
| Peak serum concentration at steady state (Cmaxss) of Nivolumab and Relatlimab |  | Up to 4 months | 
| Time-averaged serum concentration at steady state (Cavgss) of Nivolumab and Relatlimab |  | Up to 4 months | 
| Duration of Response (DOR) by BICR per RECIST v1.1 |  | Up to approximately 3 years | 
| Disease Control Rate (DCR) by BICR per RECIST v1.1 |  | Up to approximately 3 years | 
| Time to Response (TTR), by BICR per RECIST v1.1 |  | Up to approximately 3 years | 
| Objective Response Rate (ORR) by Investigator per RECIST v1.1 |  | Up to approximately 3 years | 
| DOR by Investigator per RECIST v1.1 |  | Up to approximately 3 years | 
| DCR by Investigator per RECIST v1.1 |  | Up to approximately 3 years | 
| TTR by Investigator per RECIST v1.1 |  | Up to approximately 3 years | 
| Progression Free Survival (PFS) by BICR and Investigator per RECIST v1.1 |  | Up to approximately 3 years | 
| Overall Survival |  | Up to approximately 3 years | 
| Number of Participants with Adverse Events (AEs) |  | Up to approximately 3 years | 
| Change from Baseline in Functional Assessment of Cancer Therapy - Melanoma Subscale (FACT-MS) |  | Up to approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FDC, Nivolumab, Relatlimab, Melanoma, rHuPH20, OPDUALAG