A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)
Pembrolizumab: Pembrolizumab 400 mg administered Q6W via IV infusion
Belzutifan: Belzutifan 120 mg administered QD via oral tablet
Pembrolizumab/Quavonlimab: Pembrolizumab/quavonlimab is a co-formulated product composed of pembrolizumab 400 mg in combination with quavonlimab 25 mg, administered Q6W via IV infusion
Lenvatinib: Lenvatinib 20 mg administered QD via oral capsule
Study summary
The goal of this study is to evaluate the efficacy and safety of pembrolizumab plus belzutifan plus lenvatinib or pembrolizumab/quavonlimab plus lenvatinib versus pembrolizumab plus lenvatinib as first-line treatment in participants with advanced clear cell renal cell carcinoma (ccRCC).
The primary hypotheses are (1) pembrolizumab plus belzutifan plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to progression-free survival (PFS) and overall survival (OS), in advanced ccRCC participants; and (2) pembrolizumab/quavonlimab plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to PFS and OS, in advanced ccRCC participants.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Has histologically confirmed diagnosis of RCC with clear cell component.
* Has received no prior systemic therapy for advanced ccRCC
* Male participants are abstinent from heterosexual intercourse or agree to use contraception during and for at least 7 days after last dose of study intervention with belzutifan and lenvatinib.
* Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) or use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after pembrolizumab or pembrolizumab/quavonlimab or for at least 30 days after last dose of lenvatinib or belzutifan, whichever occurs last
* Has adequately controlled blood pressure with or without antihypertensive medications
* Has adequate organ function.
* Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks prior to randomization/allocation
Exclusion Criteria:
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has had major surgery, other than nephrectomy within 4 weeks prior to randomization
* Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has received prior radiotherapy within 2 weeks prior to first dose of study intervention
* Has hypoxia or requires intermittent supplemental oxygen or requires chronic supplemental oxygen
* Has clinically significant cardiac disease within 12 months from first dose of study intervention
* Has a history of interstitial lung disease
* Has symptomatic pleural effusion; a participant who is clinically stable following treatment of this condition is eligible
* Has preexisting gastrointestinal or non-gastrointestinal fistula
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
* Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed
* Has an active autoimmune disease that has required systemic treatment in the past 2 years
* Has a history of noninfectious pneumonitis that required steroids or has current pneumonitis
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known history of Hepatitis B
* Has radiographic evidence of intratumoral cavitation, encasement or invasion of a major blood vessel
* Has clinically significant history of bleeding within 3 months prior to randomization
* Has had an allogenic tissue/solid organ transplant
Primary outcome measure(s)
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) — Up to approximately 46 months PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR based on RECIST 1.1 will be presented.
Overall Survival (OS) — Up to approximately 66 months OS is defined as the time from randomization to death due to any cause.
Trial sites (262)
Facility
City
Region
Status
The University of Alabama at Birmingham ( Site 0010)
Birmingham
Alabama
UC San Diego ( Site 0050)
La Jolla
California
Cedars Sinai Medical Center ( Site 0027)
Los Angeles
California
University of California Irvine ( Site 0029)
Orange
California
UCLA Hematology Oncology Santa Monica ( Site 0048)
Santa Monica
California
Hartford Hospital ( Site 0024)
Hartford
Connecticut
Advent Health Hematology & Oncology ( Site 0003)
Orlando
Florida
University Cancer & Blood Center, LLC ( Site 0057)
Athens
Georgia
Emory University Winship Cancer Institute ( Site 0012)
Atlanta
Georgia
Rush University Medical Center ( Site 0040)
Chicago
Illinois
Parkview Cancer Institute ( Site 0088)
Fort Wayne
Indiana
Norton Cancer Institute - St. Matthews ( Site 0065)
Louisville
Kentucky
Ochsner Medical Center ( Site 0049)
New Orleans
Louisiana
New England Cancer Specialists ( Site 0082)
Scarborough
Maine
Massachusetts General Hospital ( Site 0094)
Boston
Massachusetts
Beth Israel Deaconess Medical Center ( Site 0089)
Boston
Massachusetts
Dana Farber Cancer Institute ( Site 0093)
Boston
Massachusetts
Lahey Hospital & Medical Center ( Site 0090)
Burlington
Massachusetts
Henry Ford Hospital ( Site 0038)
Detroit
Michigan
Cancer & Hematology Centers of Western Michigan ( Site 0018)
Grand Rapids
Michigan
HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0005)
Saint Louis Park
Minnesota
Regions Hospital ( Site 0095)
Saint Paul
Minnesota
University of Mississippi Medical Center ( Site 0037)
Jackson
Mississippi
Dartmouth Hitchcock Medical Center ( Site 0075)
Lebanon
New Hampshire
Roswell Park Cancer Institute ( Site 0032)
Buffalo
New York
R.J. Zuckerberg Cancer Center-Medical Oncology ( Site 0013)
Lake Success
New York
Sidney Kimmel Center for Prostate and Urologic Cancers ( Site 0055)
New York
New York
Oregon Health & Science University ( Site 0071)
Portland
Oregon
Ralph H. Johnson VA Center ( Site 0073)
Charleston
South Carolina
University of Tennessee Medical Center Knoxville ( Site 0019)
Knoxville
Tennessee
Vanderbilt University Medical Center ( Site 0069)
Nashville
Tennessee
UTSW Medical Center ( Site 0015)
Dallas
Texas
Central Washington Health Services Association d/b/a Confluence Health ( Site 0061)
Wenatchee
Washington
Liverpool Hospital ( Site 4006)
Liverpool
New South Wales
Macquarie University ( Site 4007)
Macquarie University
New South Wales
Lyell McEwin Hospital ( Site 4004)
Elizabeth Vale
South Australia
Monash Health ( Site 4008)
Clayton
Victoria
Fiona Stanley Hospital ( Site 4009)
Murdock
Western Australia
Oncocentro Ceara ( Site 0309)
Fortaleza
Ceará
Centro de Pesquisas Clinicas em Oncologia ( Site 0306)
Cachoeiro de Itapemirim
Espírito Santo
+ 222 more sites — see the full list on the official registry below.
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time on our Cookie Policy page. See also our Privacy Policy.