Study of Pembrolizumab (MK-3475) Monotherapy in Locally Advanced/Metastatic Renal Cell Carcinoma (MK-3475-427/KEYNOTE-427)
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Pembrolizumab
Intervention description: IV infusion
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 275.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1(PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Summary:

      The purpose of this study is to assess the safety and efficacy of monotherapy pembrolizumab
      (MK-3475) in participants with renal cell carcinoma (RCC). There will be two cohorts in this
      study: Cohort A will consist of participants with clear cell (cc) RCC and Cohort B will
      consist of participants with non-clear cell (ncc) RCC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Cohort A (clear cell RCC cohort) participant must have histologically confirmed
             diagnosis of clear cell RCC or RCC with clear cell component (with or without
             sarcomatoid features).

          -  Cohort B (non-clear cell RCC cohort) participant must have histologically confirmed
             diagnosis of non-clear cell RCC (with or without sarcomatoid features). Participants
             with tumors that have a component of clear cell histology are not eligible for
             inclusion in Cohort B.

          -  Has locally advanced/metastatic disease, i.e., newly diagnosed Stage IV RCC per
             American Joint Committee on Cancer (AJCC) or have recurrent disease.

          -  Has measurable disease per RECIST 1.1 as assessed by BICR.

          -  Has received no prior systemic therapy for advanced RCC. Prior neoadjuvant/adjuvant
             therapy for RCC is acceptable if completed >12 months prior to allocation.

          -  Must provide adequate tissue for biomarker analysis for Cohorts A and B from an
             archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
             not previously irradiated.

          -  Participants receiving bone resorptive therapy (including but not limited to
             bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks prior
             to treatment allocation.

          -  Has Karnofsky Performance Status (KPS) ≥70%, as assessed within 10 days prior to
             treatment allocation.

          -  Demonstrates adequate organ function.

          -  Female participants of childbearing potential must be willing to use an adequate
             method of contraception for the course of the study through 120 days after the last
             dose of study drug.

          -  Male participants of childbearing potential 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:

          -  Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device within 4 weeks prior to allocation, has had
             major surgery within 4 weeks or radiation therapy within 2 weeks prior to allocation,
             or who has not recovered (i.e., ≤ Grade 1 or to Baseline) from AEs due to prior
             treatment.

          -  Had prior treatment with any anti-programmed cell death 1 (anti-PD-1), or
             anti-programmed cell death ligand 1 (PD-L1), or PD-L2 agent or an antibody targeting
             any other immune-regulatory receptors or mechanisms. Examples of such antibodies
             include antibodies against indoleamine-2,3-dioxygenase (IDO), PD-L1, interleukin 2
             receptors (IL-2R), glucocorticoid-induced tumor necrosis factor receptor-related
             protein (GITR).

          -  Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy
             exceeding 10 mg daily dose of prednisone or equivalent or any other form of
             immunosuppressive therapy within 7 days prior to allocation, except in the case of
             central nervous system (CNS) metastases (see below).

          -  Has an active autoimmune disease requiring systemic treatment within the past 2 years
             OR a documented history of clinically severe autoimmune disease.

          -  Has a known additional malignancy that has had progression or has required active
             treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell
             carcinoma of the skin, or carcinoma in situ, such as breast cancer in situ, that has
             undergone potentially curative therapy are acceptable.

          -  Has known active CNS metastases and/or carcinomatous meningitis.

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Has a known history of Human Immunodeficiency Virus (HIV) infection.

          -  Has known history of Hepatitis B or known active Hepatitis C.

          -  Has received a live virus vaccine within 30 days of allocation.

          -  Has had a prior solid organ transplant.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of study drug.