A Study to Compare BMS-936558 to the Physician's Choice of Either Dacarbazine or Carboplatin and Paclitaxel in Advanced Melanoma Patients That Have Progressed Following Anti-CTLA-4 Therapy (CheckMate 037)

Study Overview
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Brief Summary
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The purpose of the study is to estimate the response rate and compare overall survival of patients taking BMS-936558 to those taking study physician's choice of either Dacarbazine or Carboplatin and Paclitaxel

Official Title
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A Randomized Open-Label Phase 3 Trial of BMS-936558 (Nivolumab) Versus Investigator's Choice in Advanced (Unresectable or Metastatic) Melanoma Patients Progressing Post Anti-CTLA-4 Therapy

Conditions
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Unresectable or Metastatic Melanoma

Intervention / Treatment
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* Biological: BMS-936558
* Drug: Dacarbazine
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Men & women ≥ 18 years of age Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 Histologically confirmed Stage III (unresectable)/Stage IV melanoma Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria Objective evidence of disease progression (clinical or radiological) during or after at least 1 (V600 Wildtype) or at least 2 (V600 mutation positive) prior treatment regimens Pre-treatment fresh core, excision or punch tumor biopsy Archival Formalin-fixed paraffin-embedded (FFPE) tumor material if available Exclusion Criteria: Any treatment in a BMS-936558 (Nivolumab) trial Subjects with condition requiring systemic treatment with either corticosteroids (> 10mg daily prednisone/equivalent) or other immunosuppressive medications within 14 days of study drug administration Active, known or suspected autoimmune disease Unknown BRAF status Active brain metastasis or leptomeningeal metastasis Ocular melanoma Prior therapy with anti programmed death-1 (anti-PD-1), anti programmed death-ligand 1 (anti-PD-L1) or anti-programmed death-ligand 2 (anti-PD-L2)

Ages Eligible for Study
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Minimum Age: 18 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: BMS-936558 3 mg/kg (IV)<br>BMS-936558 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends | Biological: BMS-936558<br> <br> |
| Active Comparator: Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)<br>Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends | Drug: Dacarbazine<br> <br> * Other names: DTIC;Drug: Carboplatin<br> <br> * Other names: CBDCA;Drug: Paclitaxel<br> <br> * Other names: Onxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate (ORR) per Independent Review Committee (IRC) is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of randomized participants using RECIST 1.1 | From date of randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy (Up to approximately 38 months) | 
| Overall Survival (OS) | Overall Survival (OS) was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. Unit of measure (months) is the median survival time. | Up to 96 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented progression, as determined by the Independent Review Committee (IRC) using RECIST 1.1, or death due to any cause, whichever occurs first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment before subsequent anti-cancer therapy. Unit of measure (months) is the median survival time. | From the date of randomization to the date of the first documented progression or death (Up to approximately 38 months) | 
| Objective Response Rate (ORR) by Baseline PD-L1 Expression | Objective Response Rate (ORR) is defined as the number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) divided by number of randomized participants. PD-L1 expression evaluated for ORR. | From date of randomization to the date of objectively documented progression or the date of subsequent therapy (Up to approximately 38 months) | 
| Overall Survival (OS) by PD-L1 Positive | Overall Survival (OS) by PD-L1 expression was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. | Up to 96 months | 
| Overall Survival (OS) by PD-L1 Negative | Overall Survival (OS) by PD-L1 expression was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. | Up to 96 months | 
| Mean Change From Baseline in Health-related Quality of Life (HRQoL) | Health-related Quality of Life (HRQoL) was assessed with the EORTC QLQ-C30 questionnaire, which is the most commonly used quality-of-life instrument in oncology trials. The instrument's 30 items were divided among 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global health/quality of life scale. Raw scores for the EORTC QLQ-C30 were transformed to a 0-100 metric. Higher scores for all functional scales and Global Health Status=better HRQoL Increase from baseline indicates improvement in HRQoL. Lower scores for symptom scales=better HRQoL Decline from baseline for symptom scales =improvement in symptoms compared to baseline. A 10 point difference on a 100 point scale between treatments was considered clinically significant. | From Baseline (Day1) to second Follow-Up (Up to 96 months) |