Study of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-041/KEYNOTE-041)

Phase Ib Study of MK-3475 in Subjects With Advanced Melanoma

This study will assess the safety, tolerability, and efficacy of every-3-week dosing (Q3W) of pembrolizumab (MK-3475) in participants with advanced melanoma; participants may receive pembrolizumab for up to 2 years if deriving clinical benefit. The primary study hypothesis is that treatment with single agent pembrolizumab will result in a clinically meaningful overall response rate.

Participants who discontinue pembrolizumab after achieving a complete response (CR) and subsequently develop progressive disease (PD) may be eligible to enter a Second Course Phase and receive pembrolizumab again.

The end of the study for each participant will occur with: 1) the marketing approval of pembrolizumab for melanoma, 2) the completion of safety follow up or 3) the time when a possibility of entry to second course of treatment is lost, whichever occurs last.

Inclusion criteria:

• Histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma not amenable to local therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• At least one measurable lesion
• Adequate organ function

Exclusion criteria:

• Prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD ligand-1 (PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent
• Is currently participating or has participated in a study with an investigational compound or device within 30 days, or 5X half-life of the investigational compound, whichever is longer, of initial dosing on this study
• Chemotherapy, targeted small molecule therapy, radiotherapy, or biological cancer therapy (including monoclonal antibodies) within 4 weeks prior to the first dose of trial treatment, or not recovered (<= Grade 1 or baseline) from adverse events due to a previously administered agent
• Expected to require any other form of systemic or localized antineoplastic therapy while in study
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
• Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study treatment
• Received a live vaccine within 4 weeks prior to the first dose of trial treatment
• Has a known hypersensitivity to the components of the study drug or another monoclonal antibody
• History or evidence of active pneumonitis
• Human immunodeficiency virus (HIV)-positive
• Has known history of active Hepatitis B or C
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial treatment through 120 days after the last dose of study medication