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Clinical Trials in the UK / NCT04586231
Active, not recruiting Phase 3

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

NCT04586231 · tracked via the Priya Life Science UK tracker
Sponsor
Merck Sharp & Dohme LLC
Phase
Phase 3
Started
2021-02-25
Last updated
2026-05-05

Condition(s) studied

Carcinoma, Renal Cell

Investigational drug(s) / intervention(s)

BelzutifanLenvatinibCabozantinib

Belzutifan: Immediate-release 40 mg tablet

Lenvatinib: Capsule available in 4 mg and 10 mg dosages

Cabozantinib: Tablet available in 20 mg, 40 mg and 60 mg dosages

Study summary

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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Primary outcome measure(s)

Trial sites (184)

FacilityCityRegionStatus
Ironwood Cancer & Research Centers ( Site 0077) Chandler Arizona
Cedars Sinai Medical Center ( Site 0027) Los Angeles California
UCLA Hematology/Oncology - Santa Monica ( Site 0048) Los Angeles California
St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0095) Orange California
University of California, Irvine ( Site 0029) Orange California
Providence Saint John's Health Center ( Site 0083) Santa Monica California
Georgetown University Medical Center ( Site 0006) Washington D.C. District of Columbia
AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0003) Orlando Florida
Orlando Health, Inc. ( Site 0035) Orlando Florida
University Cancer & Blood Center, LLC ( Site 0057) Athens Georgia
Emory University Hospital ( Site 0012) Atlanta Georgia
Rush University Medical Center ( Site 0040) Chicago Illinois
Illinois Cancer Care, PC ( Site 0008) Peoria Illinois
Parkview Cancer Institute ( Site 0088) Fort Wayne Indiana
Norton Cancer Institute - St. Matthews ( Site 0065) Louisville Kentucky
Tulane University School of Medicine ( Site 0098) New Orleans Louisiana
Lahey Hospital & Medical Center ( Site 0090) Burlington Massachusetts
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
University of Mississippi Medical Ctr ( Site 0037) Jackson Mississippi
Cancer Partners of Nebraska ( Site 0086) Lincoln Nebraska
Rutgers Cancer Institute of New Jersey ( Site 0078) New Brunswick New Jersey
R.J. Zuckerberg Cancer Center-Medical Oncology ( Site 0013) Lake Success New York
Memorial Sloan Kettering Cancer Center ( Site 0055) New York New York
Levine Cancer Institute ( Site 0004) Charlotte North Carolina
Duke Cancer Institute ( Site 0096) Durham North Carolina
Lehigh Valley Hospital- Cedar Crest-Oncology Clinical Trials ( Site 0056) Allentown Pennsylvania
University of Texas, Southwestern Medical Center ( Site 0015) Dallas Texas
Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 7001) Salt Lake City Utah
University of Vermont Medical Center ( Site 0001) Burlington Vermont
Blue Ridge Cancer Care - Roanoke ( Site 0043) Roanoke Virginia
Seattle Cancer Care Alliance-Renal/Melanoma/MCC ( Site 0093) Seattle Washington
Central Washington Health Services Association d/b/a Confluence Health ( Site 0061) Wenatchee Washington
Centro de Urología (CDU) ( Site 0803) CABA Buenos Aires
Hospital Británico de Buenos Aires-Oncology ( Site 0801) Ciudad Autónoma de Buenos Aires Buenos Aires
Instituto Alexander Fleming ( Site 0800) Ciudad Autónoma de Buenos Aires Buenos Aires
Asociación de Beneficencia Hospital Sirio Libanés ( Site 0804) Buenos Aires Buenos Aires F.D.
Sanatorio Británico-Clinical Oncology Department ( Site 0802) Rosario Santa Fe Province
Sanatorio Parque ( Site 0806) Rosario Santa Fe Province
GenesisCare North Shore ( Site 4011) St Leonards New South Wales

+ 144 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.

View NCT04586231 on ClinicalTrials.gov ↗ ← All trials in the UK