A Phase III Randomized, Open-label Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy as a First-line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-426)


Condition: Renal Cell Carcinoma

Intervention:

  • Biological: Pembrolizumab
  • Drug: Axitinib
  • Drug: Sunitinib

Purpose: The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475) in combination with axitinib versus sunitinib monotherapy as a first-line treatment for participants with advanced/metastatic renal cell carcinoma (mRCC). The primary hypotheses of this study are: 1) The combination therapy of pembrolizumab plus axitinib is superior to sunitinib monotherapy with respect to Progression-Free Survival (PFS) as assessed by blinded independent central imaging review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and 2) the combination therapy of pembrolizumab plus axitinib is superior to sunitinib monotherapy with respect to Overall Survival (OS).

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02853331

Sponsor: Merck Sharp & Dohme Corp.

Primary Outcome Measures:

  • Measure: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review
  • Time Frame: Up to approximately 2 years
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: Up to approximately 39 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Independent Central Imaging Review
  • Time Frame: Up to approximately 2 years
  • Safety Issue:
  • Measure: Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by Blinded Independent Central Imaging Review
  • Time Frame: Up to approximately 2 years
  • Safety Issue:
  • Measure: Number of Participants Who Experience an Adverse Event (AE)
  • Time Frame: Up to approximately 39 months
  • Safety Issue:
  • Measure: Number of Participants Who Discontinue Study Drug Due to an AE
  • Time Frame: Up to approximately 39 months
  • Safety Issue:
  • Measure: Duration of Response (DOR) Per RECIST 1.1 as Assessed by Blinded Independent Central Imaging Review
  • Time Frame: Up to approximately 2 years
  • Safety Issue:

Estimated Enrollment: 840

Study Start Date: September 16, 2016

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Has histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features.
  • Has locally advanced/metastatic disease (i.e., newly diagnosed Stage IV RCC per American Joint Committee on Cancer) or has recurrent disease.
  • Has measurable disease per RECIST 1.1 as assessed by the investigator/site radiologist.
  • Has received no prior systemic therapy for advanced RCC.
  • Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
  • Has Karnofsky performance status (KPS) ≥ 70% as assessed within 10 days prior to randomization.
  • If receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks prior to randomization.
  • 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 has used an investigational device within 4 weeks prior to randomization.
  • Has had major surgery within 4 weeks, received radiation therapy within 2 weeks prior to randomization, or has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to prior treatment.
  • Has had prior treatment with any anti-programmed cell death (anti-PD-1), or programmed cell death ligand 1 (PD-L1), or PD-L2 agent or an antibody targeting any other immune-regulatory receptors or mechanisms.
  • Has received prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR) or mechanistic target of rapamycin (mTOR) targeting agents.
  • Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to axitinib or sunitinib.
  • Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy exceeding physiologic corticosteroid dose or any other form of immunosuppressive therapy within 7 days prior to randomization, except in the case of central nervous system (CNS) metastases.
  • Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease. Note: Participants with vitiligo, Sjøgren's syndrome, Type 1 diabetes, resolved childhood asthma/atopy, hypothyroidism or adrenal or pituitary insufficiency who are stable on hormone replacement, are not excluded.
  • Has a known additional malignancy that has progressed or has required active treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ such as breast cancer in situ are acceptable if they have undergone potentially curative therapy.
  • 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).
  • Has known active Hepatitis B or Hepatitis C infection.
  • Has received a live virus vaccine within 30 days of randomization.
  • Has a clinically significant gastrointestinal (GI) abnormality including:
  • Malabsorption, total gastric resection
  • Or any condition that might affect the absorption of orally taken medication
  • Active GI bleeding, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy
  • Intraluminal metastatic lesion with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other GI condition associated with increased risk of perforation
  • Has QT interval corrected for heart rate (QTc) ≥480 msec.
  • Has a history of any of the following cardiovascular conditions within 12 months of randomization:
  • Myocardial infarction
  • Unstable angina pectoris
  • Cardiac angioplasty or stenting
  • Coronary/peripheral artery bypass graft
  • Class III or IV congestive heart failure per New York Heart Association
  • Cerebrovascular accident or transient ischemic attack
  • Has a history of deep vein thrombosis or pulmonary embolism within 6 months of screening.
  • Has poorly controlled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg.
  • Has evidence of inadequate wound healing.
  • Has active bleeding disorder or other history of significant bleeding episodes within 30 days of randomization.
  • Has hemoptysis within 6 weeks prior to randomization.
  • Has current use (within 7 days of randomization) or anticipated need for treatment with drugs or foods that are known strong cytochrome P450 (CYP3A4/5) inhibitors.
  • Has current use (within 7 days of randomization) or anticipated need for treatment with drugs that are known strong CYP3A4/5 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort; or drugs that are known with proarrhythmic potential.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • 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 0086)
  • Orange California 92868 United States
  • Call for Information (Investigational Site 8001)
  • Denver Colorado 80218 United States
  • Call for Information (Investigational Site 0095)
  • Washington District of Columbia 20007 United States
  • Call for Information (Investigational Site 0091)
  • Marietta Georgia 30060 United States
  • Call for Information (Investigational Site 0078)
  • Chicago Illinois 60611 United States
  • Call for Information (Investigational Site 0041)
  • Chicago Illinois 60612 United States
  • Call for Information (Investigational Site 0035)
  • New Orleans Louisiana 70121 United States
  • Call for Information (Investigational Site 0046)
  • Lincoln Nebraska 68510 United States
  • Call for Information (Investigational Site 0088)
  • Buffalo New York 14263 United States
  • Call for Information (Investigational Site 0032)
  • New York New York 10016 United States
  • Call for Information (Investigational Site 0020)
  • Rochester New York 14642 United States
  • Call for Information (Investigational Site 0087)
  • Charlotte North Carolina 28204 United States
  • Call for Information (Investigational Site 0805)
  • Cleveland Ohio 44111 United States
  • Call for Information (Investigational Site 0009)
  • Cleveland Ohio 44195 United States
  • Call for Information (Investigational Site 0806)
  • Mayfield Heights Ohio 44124 United States
  • Call for Information (Investigational Site 0037)
  • Portland Oregon 97239 United States
  • Call for Information (Investigational Site 8010)
  • Tualatin Oregon 97062 United States
  • Call for Information (Investigational Site 0093)
  • Allentown Pennsylvania 18103 United States
  • Call for Information (Investigational Site 0013)
  • Philadelphia Pennsylvania 19111 United States
  • Call for Information (Investigational Site 0062)
  • Pittsburgh Pennsylvania 15232 United States
  • Call for Information (Investigational Site 8004)
  • Charleston South Carolina 29414 United States
  • Call for Information (Investigational Site 0089)
  • Sioux Falls South Dakota 57104 United States
  • Call for Information (Investigational Site 0090)
  • Chattanooga Tennessee 37403 United States
  • Call for Information (Investigational Site 0070)
  • Germantown Tennessee 38138 United States
  • Call for Information (Investigational Site 0064)
  • Dallas Texas 75390 United States
  • Call for Information (Investigational Site 8002)
  • Houston Texas 77024 United States
  • Call for Information (Investigational Site 8003)
  • San Antonio Texas 78217 United States
  • Call for Information (Investigational Site 0072)
  • Salt Lake City Utah 84106 United States
  • Call for Information (Investigational Site 0082)
  • Fairfax Virginia 22031 United States
  • MSD Brasil
  • Sao Paulo Brazil
  • Merck Canada
  • Kirkland Quebec H9H 4M7 Canada
  • MSD SRO Czech
  • Prague Prague 6 Czechia
  • MSD France
  • Paris France
  • MSD Ireland (Human Health) Ltd.
  • Dublin Ireland
  • MSD K.K.
  • Chiyoda-Ku, Tokyo 102-8667 Japan
  • MSD Korea LTD
  • Seoul 4130 Korea, Republic of
  • MSD Polska Sp. Z o.o.
  • Warsaw Poland
  • Merck Sharp and Dohme de Espana S.A.
  • Madrid Spain
  • MSD Ukraine LLC
  • Kiev Ukraine
  • Merck Sharp & Dohme Ltd.
  • Hoddesdon United Kingdom

View trial on ClinicalTrials.gov


E-Newsletters

Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.

Subscribe