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

Disease Control Rate (ORR) Per BICR

Disease control rate (DCR) is defined as the percentage of participants who achieve a BOR of confirmed Complete Response (CR), confirmed Partial Response (PR), or stable disease (SD), based on BICR assessments (using RECIST 1.1) divided by the number of all randomized participants. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of target lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study.

Time frame: 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 126 weeks)

Time to Response (TTR) Per BICR

Time to response (TTR) assessed by BICR is defined as the time between the date of randomization and the first confirmed documented response (CR or PR) per RECIST 1.1 criteria. 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.

Time frame: 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 126 weeks)

Duration of Response (DoR) Per BICR

Duration of Response (DOR) in months is defined as the time from date of the first documentation of objective response (CR or PR) to the first documentation of PD or to death due to any cause in the absence of documented PD. CR is complete disappearance of all target lesions except nodal disease; all target nodes must decrease to normal size (short axis \< 10 mm). PR is ≥30% decrease under baseline of the sum of diameters of all target measurable lesions. Disease progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm.

Time frame: 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 126 weeks)

Progression Free Survival Per BICR

Progression free survival (PFS) is defined as time from on treatment to disease progression or death (whichever comes first). 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.

Time frame: 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 126 weeks)

Objective Response Rate (ORR) Per Investigator

Objective response rate (ORR) is defined as the percentage of participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on Investigator assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), 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.

Time frame: 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 126 weeks)

Disease Control Rate (ORR) Per Investigator

Disease control rate (DCR) is defined as the percentage of participants who achieve a BOR of confirmed Complete Response (CR), confirmed Partial Response (PR), or stable disease (SD), based on Investigator assessments (using RECIST 1.1) divided by the number of all randomized participants. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of target lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study.

Time frame: 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 126 weeks)

Time to Response (TTR) Per Investigator

Time to response (TTR) assessed by Investigator is defined as the time between the date of randomization and the first confirmed documented response (CR or PR) per RECIST 1.1 criteria. 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.

Time frame: 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 126 weeks)

Duration of Response (DoR) Per Investigator

Duration of Response (DOR) in months is defined as the time from date of the first documentation of objective response (CR or PR) to the first documentation of PD or to death due to any cause in the absence of documented PD. CR is complete disappearance of all target lesions except nodal disease; all target nodes must decrease to normal size (short axis \< 10 mm). PR is ≥30% decrease under baseline of the sum of diameters of all target measurable lesions. Disease progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm.

Time frame: 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 126 weeks)

Progression Free Survival Per Investigator

Progression free survival (PFS) is defined as time from on treatment to disease progression or death (whichever comes first). 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.

Time frame: 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 126 weeks)

Overall Survival (OS)

Overall survival is defined as the time from the first dosing date (or from randomization/on treatment) to the date of death from any cause. Median computed using Kaplan-Meier method.

Time frame: 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 126 weeks)

Trough Serum Concentration of Nivolumab and Relatlimab (Cmind28) at Day 28

Blood samples were collected to assess serum concentration.

Time frame: Pre-dose at Day 28

Peak Serum Concentration (Cmax1) After the First Dose of Nivolumab and Relatlimab

Blood samples were collected to assess serum concentration.

Time frame: Post-dose Day 1

Maximum Observed Concentration at Steady State (Cmaxss) Nivolumab and Relatlimab

Blood samples were collected to assess serum concentration.

Time frame: Post-dose Day 1

Average Observed Concentration at Steady State (Cavgss) of Nivolumab and Relatlimab

Blood samples were collected to assess serum concentration.

Time frame: Post-dose Day 1

Number of Participants With Adverse Events, SAEs, AEs Leading to Discontinuation and Deaths

AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence at any dose that: results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions, results in a congenital abnormality or birth defect, or is an important medical event that may not result in death, be life-threatening, or require hospitalization, but may require medical or surgical intervention to prevent any of the outcomes listed above.

Time frame: First dose (Day 1) and 30 days after last dose of study therapy (up to approximately 26 months)

Number of Participants With Immune-mediate Adverse Events (IMAEs)

AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment.

Time frame: First dose (Day 1) and 135 days after last dose of study therapy (up to approximately 29 months)

Number of Participants With Other Event of Special Interest (OESI)

AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment.

Time frame: First dose (Day 1) and 100 days after last dose of study therapy (up to approximately 28 months)

Number of Participants With On-Treatment Worst CTCAE Grade 3-4 Laboratory Parameters

AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment.

Time frame: First dose (Day 1) and 30 days after last dose of study therapy (up to approximately 26 months)

Change From Baseline Functional Assessment of Cancer Therapy -Melanoma (FACT-M) Total Score

The FACT-M questionnaire was used to assess the effects of disease symptoms on functioning and well-being. As a generic cancer-related core, the FACT-M includes the 27-item FACT General (FACT-G) to assess physical well-being (PWB; 7 items), social/family well-being (SWB; 7 items), emotional well-being (EWB; 6 items), and functional well-being (FWB; 7 items). In addition, the FACT-M includes a 16-item disease-specific Melanoma Subscale (MS). Each FACT-M item is rated on a 5-point scale ranging from 0 (not at all) to 4 (very much). Scores for the PWB, FWB, SWB, and EWB subscales can be combined to produce a FACT-G total score, which provides an overall indicant of generic quality of life, while the FACT-G and MS scores can be combined to produce a total score for the FACT-M, which provides a composite measure of general and targeted quality of life. Overall scale ranges from 0 to 172, higher values indicate better functioning as well as lower symptom burden.

Time frame: Baseline (Day 1) and Week 85