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

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

All AEs: Up to 30 days after last dose of study drug; Serious AEs: Up to 90 days after last dose of study drug (Up to 27 months)

Safety Population: All participants who received ≥1 dose of study drug. Per protocol, disease progression of cancer under study was not considered an adverse event (AE) unless considered related to study drug. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.