A Single-Arm, Open-Label, Multicenter Clinical Trial with Nivolumab (BMS-936558) for Subjects with Histologically Confirmed Stage III (unresectable) or Stage IV Melanoma Progressing Post Prior Treatment Containing an Anti-CTLA-4 Monoclonal Antibody

Study Objective

The primary objectives of this trial is:

• To determine the rate and frequency of high-grade (CTCAE v4.0 Grade 3 or higher), treatment-related, select adverse events in subjects with histologically confirmed stage III (unresectable) or stage IV melanoma and progression post prior treatment containing an anti-CTLA-4 monoclonal antibody, treated with nivolumab (BMS-936558) at a dose of 3 mg/kg every two weeks for a maximum of 24 months.

The secondary objectives of this study are:

• To characterize the outcome (duration of treatment and grade of resolution) of high-grade (CTCAE v4.0 Grade 3 or higher), select adverse events in subjects with histologically confirmed stage III (unresectable) or stage IV melanoma and progression post prior treatment containing an anti-CTLA-4 monoclonal antibody, treated with nivolumab (BMS-936558) at a dose of 3 mg/kg every 2 weeks for a maximum of 24 months.
• To estimate overall survival (OS) in all treated subjects
• To estimate Investigator-assessed best overall response (BOR)

The exploratory objectives in this study are to:

• To assess safety, tolerability, OS, and Investigator-assessed BOR in patients with BRAF-mutated melanoma, patients with inactive brain metastases, Performance Status 2, or uveal/ocular or mucosal melanoma.
• To assess OS and Investigator-assessed BOR in patients progressing during (the period from the first to last dose of anti-CTLA-4 plus 3 weeks) versus after treatment with an anti-CTLA-4 monoclonal antibody
• To assess OS and Investigator-assessed BOR in patients experiencing objective response (complete response, partial response) or stable disease under treatment with an anti-CTLA-4 monoclonal antibody versus patients having no objective response or stable disease
• To assess Quality of Life (QoL)

Participation conditions

Key Inclusion criteria

• Subjects with histologically confirmed malignant melanoma
• Eastern Cooperative Oncology Group (ECOG) Performance Status:
  • PS 0 to 1 (Cohort 1)
  • PS 2 (Cohort 2; maximum of 300; clinical risk benefit ratio of Cohort 2 will be monitored by the Scientific Steering Committee and evaluated after treatment of n = 50 for at least 2 months)
• Previously treated unresectable stage III or stage IV melanoma as per the American Joint Committee on Cancer 2010 Guidelines regardless of BRAF mutation status
• Subjects must have experienced evaluable RECIST 1.1-defined disease progression
• Prior treatment with chemotherapy, interferon (adjuvant setting), IL-2, BRAF/MEK inhibitors for subjects with known BRAF mutations, MEK inhibitors for NRAS mutations, and cKIT inhibitor subjects with known cKIT mutations are allowed

Key Exclusion criteria

• Leptomeningeal metastases are excluded
• Subjects with untreated, active CNS metastases are excluded

Centre hospitalier de Luxembourg