A Phase II Single-arm, Open-label Monotherapy Clinical Trial of Pembrolizumab (MK-3475) in Locally Advanced/Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-427)


Condition: Renal Cell Carcinoma

Intervention:

  • Biological: Pembrolizumab

Purpose: 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02853344

Sponsor: Merck Sharp & Dohme Corp.

Primary Outcome Measures:

  • Measure: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
  • Time Frame: Up to 24 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Duration of Response (DOR) per RECIST 1.1 as assessed by BICR
  • Time Frame: Up to 24 months
  • Safety Issue:
  • Measure: Disease Control Rate (DCR) per RECIST 1.1 as assessed by BICR
  • Time Frame: Up to 24 months
  • Safety Issue:
  • Measure: Progression-free Survival (PFS) per RECIST 1.1 as assessed by BICR
  • Time Frame: Up to 24 months
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: Up to 24 months
  • Safety Issue:
  • Measure: Number of Participants Who Experience an Adverse Event (AE)
  • Time Frame: Up to 27 months
  • Safety Issue:
  • Measure: Number of Participants Who Discontinue Study Drug Due to an AE
  • Time Frame: Up to 24 months
  • Safety Issue:

Estimated Enrollment: 255

Study Start Date: September 30, 2016

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

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.

Contact:

  • Toll Free Number
  • 1-888-577-8839

Locations:

  • Call for Information (Investigational Site 8005)
  • Tucson Arizona 85711 United States
  • Call for Information (Investigational Site 0094)
  • San Francisco California 94158 United States
  • Call for Information (Investigational Site 0095)
  • Washington District of Columbia 20007 United States
  • Call for Information (Investigational Site 0049)
  • Washington District of Columbia 20037 United States
  • Call for Information (Investigational Site 8007)
  • Miami Florida 33143 United States
  • Call for Information (Investigational Site 0053)
  • Chicago Illinois 60637 United States
  • Call for Information (Investigational Site 0050)
  • New Orleans Louisiana 70112 United States
  • Call for Information (Investigational Site 0096)
  • Boston Massachusetts 02215 United States
  • Call for Information (Investigational Site 0017)
  • Detroit Michigan 48202 United States
  • Call for Information (Investigational Site 0014)
  • Billings Montana 59102 United States
  • Call for Information (Investigational Site 8009)
  • Las Vegas Nevada 89169 United States
  • Call for Information (Investigational Site 0032)
  • New York New York 10016 United States
  • Call for Information (Investigational Site 0099)
  • Philadelphia Pennsylvania 19111 United States
  • Call for Information (Investigational Site 8008)
  • Charleston South Carolina 29414 United States
  • Call for Information (Investigational Site 0090)
  • Chattanooga Tennessee 37403 United States
  • Call for Information (Investigational Site 0093)
  • Burlington Vermont 05401 United States
  • Call for Information (Investigational Site 8006)
  • Roanoke Virginia 24014 United States
  • Call for Information (Investigational Site 0021)
  • Kennewick Washington 99336 United States
  • Call for Information (Investigational Site 0026)
  • Milwaukee Wisconsin 53226 United States
  • MSD SRO Czech
  • Prague Prague 6 Czechia
  • Merck Sharp & Dohme
  • Glostrup Denmark
  • MSD Polska Sp. Z o.o.
  • Warsaw Poland
  • Merck Sharp & Dohme IDEA, Inc.
  • Moscow Russian Federation
  • Merck Sharp and Dohme de Espana S.A.
  • Madrid Spain
  • Merck Sharp & Dohme Ltd.
  • Hoddesdon United Kingdom

View trial on ClinicalTrials.gov


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