Study to Evaluate the Safety and Efficacy of Two Different Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Participants With Advanced Melanoma (MK-3475-006/KEYNOTE-006)
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Pembrolizumab; Ipilimumab
Intervention description: 10 mg/kg IV, administered Q2W or Q3W based upon randomization.; 3 mg/kg IV Q3W.
Intervention MeSH terms: Pembrolizumab; Ipilimumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 834.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Summary:

      This study will evaluate the safety and efficacy of 2 different dosing schedules of
      pembrolizumab (MK-3475), every 2 weeks (Q2W) and every 3 weeks (Q3W), and compare the 2
      schedules to treatment with ipilimumab in ipilimumab-naïve participants with unresectable or
      metastatic melanoma. The primary hypotheses are that pembrolizumab is superior to ipilimumab
      with respect to progression-free survival (PFS) and overall survival (OS).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically-confirmed diagnosis of unresectable Stage III or metastatic melanoma
             not amenable to local therapy (excluding uveal or ocular melanoma)

          -  At least one measurable lesion

          -  No prior systemic treatment (excluding adjuvant or neoadjuvant therapy) for melanoma
             (first line) or one prior systemic treatment (excluding adjuvant or neoadjuvant
             therapy) for melanoma (second line)

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Archived tissue sample or new biopsy sample

          -  Female participants of childbearing potential must agree to use effective
             contraception from Visit 1 to 120 days after the last dose of study drug; male
             participants must agree to use an adequate method of contraception starting with the
             first dose of study drug through 120 days after the last dose of study drug

        Exclusion criteria:

          -  Prior treatment with ipilimumab or other anti-cytotoxic T-Lymphocyte Antigen 4
             (CTLA-4) agent or any anti-programmed cell death (PD-1 or PD-L2) agent

          -  Chemotherapy, radioactive, or biological cancer therapy within four weeks prior to the
             first dose of study drug, or not recovered from adverse events caused by cancer
             therapeutics administered more than four weeks earlier

          -  Currently participating or has participated in a study of an investigational agent or
             using an investigational device within 30 days of the first dose of study drug

          -  Expected to require any other form of systemic or localized antineoplastic therapy
             while on study

          -  On any systemic steroid therapy within one week before the planned date for first dose
             of randomized treatment or on any other form of immunosuppressive medication

          -  History of a malignancy (other than the disease under treatment in the study) within 5
             years prior to first study drug administration, excluding adequately treated Stage 1
             or Stage 2 basal/squamous cell carcinoma of the skin, carcinoma in situ of the cervix
             or breast, or other in situ cancers.

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis;
             participants with previously treated brain metastases are eligible

          -  Severe hypersensitivity reaction to treatment with another monoclonal antibody

          -  Active autoimmune disease or a documented history of autoimmune disease or syndrome
             that requires systemic steroids or immunosuppressive agents

          -  Active infection requiring systemic therapy

          -  Known history of Human Immunodeficiency Virus (HIV)

          -  Known history of or positive for Hepatitis B or C

          -  Known psychiatric or substance abuse disorder

          -  Regular user (including recreational use) of illicit drugs or had a recent history
             (within the last year) of substance abuse (including alcohol)

          -  Pregnant or breastfeeding, or expecting to conceive, or father children within the
             projected duration of the study

          -  Received a live vaccine within 30 days prior to first dose of study drug