A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)

Running, not enrolling · Phase 3

Conditions studied: Carcinoma, Renal Cell

In brief

This study will compare the efficacy and safety of belzutifan + lenvatinib versus cabozantinib in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy. The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival.

Key facts

Study ID: NCT04586231
Run by: Merck Sharp & Dohme LLC
People needed: 747
Starts: 2021-02-25
Expected to finish: 2027-02-11
Last updated by the study team: 2026-05-05

Who can join

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

You may qualify if…

Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment or neoadjuvant/adjuvant with progression on or within 6 months of last dose.
Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.
Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization.
Received no more than 2 prior systemic regimens including: one anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with progression on or within 6 months from the last dose of that regimen OR one or 2 regimens for locoregional/advanced disease
Received only 1 prior antiPD-1/L1 therapy for adjuvant, neoadjuvant/adjuvant or locally advanced/metastatic RCC.
A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib.
A female participant is eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention in the belzutifan+ lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm.
Adequately controlled blood pressure.
Adequate organ function.

You may not qualify if…

A pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
Known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
Clinically significant cardiac disease within 6 months of first dose of study intervention.
Prolongation of QTc interval to >480 ms.
Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable.
Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.
Moderate to severe hepatic impairment.
History of significant bleeding within 3 months before randomization.
History of solid organ transplantation.
Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations.
Received colony-stimulating factors [eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)] within 28 days before randomization.
Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor.
Prior treatment with lenvatinib.
Prior treatment with cabozantinib.
Currently participating in a study of an investigational agent or using an investigational device.
Active infection requiring systemic therapy.
History of human immunodeficiency virus (HIV) infection.
History of hepatitis B or known active hepatitis C infection.

Where it is running

Cedars Sinai Medical Center ( Site 0027) — Los Angeles, California, United States
UCLA Hematology/Oncology - Santa Monica ( Site 0048) — Los Angeles, California, United States
St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0095) — Orange, California, United States
University of California, Irvine ( Site 0029) — Orange, California, United States
Providence Saint John's Health Center ( Site 0083) — Santa Monica, California, United States
Georgetown University Medical Center ( Site 0006) — Washington D.C., District of Columbia, United States
AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0003) — Orlando, Florida, United States
Orlando Health, Inc. ( Site 0035) — Orlando, Florida, United States
University Cancer & Blood Center, LLC ( Site 0057) — Athens, Georgia, United States
Emory University Hospital ( Site 0012) — Atlanta, Georgia, United States
Rush University Medical Center ( Site 0040) — Chicago, Illinois, United States
Illinois Cancer Care, PC ( Site 0008) — Peoria, Illinois, United States
Parkview Cancer Institute ( Site 0088) — Fort Wayne, Indiana, United States
Norton Cancer Institute - St. Matthews ( Site 0065) — Louisville, Kentucky, United States
Tulane University School of Medicine ( Site 0098) — New Orleans, Louisiana, United States
Lahey Hospital & Medical Center ( Site 0090) — Burlington, Massachusetts, 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
University of Mississippi Medical Ctr ( Site 0037) — Jackson, Mississippi, United States
Cancer Partners of Nebraska ( Site 0086) — Lincoln, Nebraska, United States
Rutgers Cancer Institute of New Jersey ( Site 0078) — New Brunswick, New Jersey, United States
R.J. Zuckerberg Cancer Center-Medical Oncology ( Site 0013) — Lake Success, New York, United States
Memorial Sloan Kettering Cancer Center ( Site 0055) — New York, New York, United States
Levine Cancer Institute ( Site 0004) — Charlotte, North Carolina, United States
Ironwood Cancer & Research Centers ( Site 0077) — Chandler, Arizona, United States

Full record on ClinicalTrials.gov

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