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)

Running, not enrolling · Phase 3

Conditions studied: Carcinoma, Renal Cell

In brief

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.

Key facts

Study ID

NCT04736706

Run by

Merck Sharp & Dohme LLC

People needed

1653

Starts

2021-04-14

Expected to finish

2026-10-29

Last updated by the study team

2026-05-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• 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

Where it is running

• UC San Diego ( Site 0050) — La Jolla, California, United States
• Cedars Sinai Medical Center ( Site 0027) — Los Angeles, California, United States
• University of California Irvine ( Site 0029) — Orange, California, United States
• UCLA Hematology Oncology Santa Monica ( Site 0048) — Santa Monica, California, United States
• Hartford Hospital ( Site 0024) — Hartford, Connecticut, United States
• Advent Health Hematology & Oncology ( Site 0003) — Orlando, Florida, United States
• University Cancer & Blood Center, LLC ( Site 0057) — Athens, Georgia, United States
• Emory University Winship Cancer Institute ( Site 0012) — Atlanta, Georgia, United States
• Rush University Medical Center ( Site 0040) — Chicago, Illinois, United States
• Parkview Cancer Institute ( Site 0088) — Fort Wayne, Indiana, United States
• Norton Cancer Institute - St. Matthews ( Site 0065) — Louisville, Kentucky, United States
• Ochsner Medical Center ( Site 0049) — New Orleans, Louisiana, United States
• New England Cancer Specialists ( Site 0082) — Scarborough, Maine, United States
• Massachusetts General Hospital ( Site 0094) — Boston, Massachusetts, United States
• Beth Israel Deaconess Medical Center ( Site 0089) — Boston, Massachusetts, United States
• Dana Farber Cancer Institute ( Site 0093) — Boston, Massachusetts, United States
• Lahey Hospital & Medical Center ( Site 0090) — Burlington, Massachusetts, United States
• Henry Ford Hospital ( Site 0038) — Detroit, Michigan, United States
• Cancer & Hematology Centers of Western Michigan ( Site 0018) — Grand Rapids, Michigan, United States
• HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0005) — Saint Louis Park, Minnesota, United States
• Regions Hospital ( Site 0095) — Saint Paul, Minnesota, United States
• University of Mississippi Medical Center ( Site 0037) — Jackson, Mississippi, United States
• Dartmouth Hitchcock Medical Center ( Site 0075) — Lebanon, New Hampshire, United States
• Roswell Park Cancer Institute ( Site 0032) — Buffalo, New York, United States
• The University of Alabama at Birmingham ( Site 0010) — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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