Inclusion criteria:

• Unresectable (Stage III) or metastatic melanoma
• Failed or progressed on standard of care systemic therapy including ipilimumab (with the exception of a participant with progressive disease while on the ipilimumab arm of MK-3475-006, regardless of prior treatment with a BRAF/MEK inhibitor, as long as all other eligibility criteria for this study are met)
• Willing to sign Informed Consent
• Eastern Cooperative Oncology Group Performance status of 0 or 1
• Female participants of childbearing potential must be willing to use adequate contraception or be surgically sterile, or abstain from heterosexual activity starting with the first dose of treatment through at least 120 days after the last dose of pembrolizumab
• Male participants must agree to use an adequate method of contraception starting with the first dose of treatment through 120 days after the last dose of pembrolizumab
• Adequate organ function

Exclusion criteria:

• Eligible for an accessible pembrolizumab clinical study or previously participated in a pembrolizumab clinical study (with the exception of a participant with progressive disease while on the ipilimumab arm of MK-3475-006)
• Eligible for treatment with a marketed BRAF inhibitor or MEK inhibitor (with the exception of a participant with progressive disease while on the ipilimumab arm of MK-3475-006, regardless of prior treatment with a BRAF/MEK inhibitor, as long as all other eligibility criteria for this study are met)
• Not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better due to prior chemotherapy, radioactive, or biological cancer therapy (including monoclonal antibodies)
• Not recovered from minor or major surgery and less than 4 weeks from major surgery
• History of life-threatening or severe immune-related adverse events on treatment with another immunotherapy
• Expected to require any other form of systemic antineoplastic therapy while receiving pembrolizumab
• History of clinically severe autoimmune disease (e.g., requires chronic immunosuppressive therapy)
• History of pneumonitis, organ transplant, human immunodeficiency virus (HIV), active hepatitis B or hepatitis C
• Active central nervous system metastases, carcinomatous meningitis, untreated brain metastases
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of treatment with pembrolizumab
• Active infection requiring systemic therapy