Study of Pembrolizumab (MK-3475) Versus Placebo After Complete Resection of High-Risk Stage III Melanoma (MK-3475-054/1325-MG/KEYNOTE-054)
Condition: Melanoma
MeSH terms: Melanoma
Intervention: pembrolizumab; placebo
Intervention description: Pembrolizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle; Normal saline solution administered IV on Day 1 of each 21-day cycle
Intervention MeSH terms: Pembrolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1019.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD-1); Programmed Cell Death 1 (PD1); Programmed Cell Death-Ligand 1 (PD-L1, PDL1); Programmed Cell Death-Ligand 2 (PD-L2, PDL2)

Summary:

      This study will assess whether post-surgery therapy with pembrolizumab improves
      recurrence-free survival (RFS) as compared to placebo for high-risk participants with
      melanoma (Stage IIIA [> 1 mm metastasis], IIIB and IIIC). The study will also assess whether
      pembrolizumab improves RFS versus placebo in the subgroup of participants with programmed
      cell death-ligand 1 (PD-L1)-positive tumor expression. Participants will be stratified for
      stage of disease and region and then will be randomly assigned to receive either
      pembrolizumab or placebo as post-surgery therapy in Part 1. In Part 2, participants who
      experience a disease recurrence are eligible for pembrolizumab treatment (if treated with
      placebo in Part 1) or pembrolizumab rechallenge (if treated with pembrolizumab in Part 1).
      Participants deriving benefit from pembrolizumab will be given the opportunity to transfer to
      a pembrolizumab extension study, if available, upon study closure, and will be monitored
      following the standard of assessments of the pembrolizumab extension study.
    

Eligibility criteria:

        Inclusion criteria:

          -  Completely resected Stage III melanoma

          -  Tumor tissue available for evaluation of PD-L1 expression

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Adequate organ function

          -  No prior therapy for melanoma except surgery for primary melanoma lesions (or
             previously treated with interferon for thick primary melanomas without evidence of
             lymph node involvement are eligible)

          -  Female participants of childbearing potential should be willing to use adequate
             methods of birth control or be surgically sterile, or abstain from heterosexual
             activity for the course of the study through 120 days after the last dose of study
             medication

          -  Male participants should agree to use an adequate method of birth control starting
             with the first dose of study therapy through 120 days after the last dose of study
             medication

        Exclusion criteria:

          -  Mucosal or ocular melanoma

          -  History of (non-infectious) pneumonitis that required steroids or current pneumonitis

          -  History of or current interstitial lung disease

          -  History of hematologic or primary solid tumor malignancy, unless no evidence of that
             disease for 5 years

          -  Active autoimmune disease that has required systemic treatment in past 2 years

          -  Active infection requiring therapy

          -  Unstable hyperthyroidism or hypothyroidism

          -  Diagnosis of immunodeficiency

          -  Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days
             prior to the first dose of study medication

          -  Known history of human immunodeficiency virus (HIV), active Hepatitis B or C

          -  Treatment with live vaccine within 30 days prior to the first dose of study medication
             are not eligible

          -  Prior treatment with any anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4)
             monoclonal antibody or anti-programmed cell death receptor 1 (PD-1), anti-programmed
             cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2
             (PD-L2) agent, or prior participation in any Merck pembrolizumab clinical trial

          -  Currently participating and receiving study therapy, or participated in a study of an
             investigational agent and received study therapy or used an investigation device
             within 4 weeks of the first dose of study medication

          -  Pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 120 days
             after the last dose of study medication

          -  Participant is or has an immediate family member (e.g., spouse, parent/legal guardian,
             sibling or child) who is investigational site or Sponsor staff directly involved with
             this trial without prospective Institutional Review Board approval (by chair or
             designee) is given