Recruiting

Phase 3

Belzutifan & ZanzalintinibA Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033)

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT07227402

Conditions

Renal Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Belzutifan

Zanzalintinib

Cabozantinib

Study Details

Brief summary:

Researchers are looking for more ways to treat advanced renal cell carcinoma (RCC) that is recurrent. Researchers want to learn if recurrent advanced renal cell carcinoma (RCC) responds (gets smaller or goes away) after treatment with belzutifan (MK-6482) and zanzalintinib compared to cabozantinib.

The goal of this study is to learn if:

People who take belzutifan and zanzalintinib live longer overall and without the cancer getting worse than people who take cabozantinib.

Conditions

Renal Cell Carcinoma

Study ID

NCT07227402

Start date

Nov 26, 2025

Status verified date

Jul, 2026

Completion date

Feb 27, 2032

Anticipated

Primary completion date

Feb 27, 2032

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

Has a histologically confirmed diagnosis of unresectable, advanced renal cell cancer (RCC) with clear cell component (with or without sarcomatoid features) i.e., Stage IV renal cell cancer per American Joint Committee on Cancer (AJCC) (8th Edition)
Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
Has disease recurrence during adjuvant anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/L1) therapy or recurrence ≤24 months following the last dose of adjuvant anti-PD-1/L1 therapy
Has received no other prior systemic therapy for their RCC except for their adjuvant anti-PD-1/L1 therapy

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, new-onset angina, pulmonary embolism, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
Had deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization
Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram
Has had major surgery within 8 weeks before randomization or has not adequately recovered from major surgery or has ongoing surgical complications
Has current pneumonitis/interstitial lung disease
Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage within 4 weeks prior to randomization
Has a gastrointestinal disorder including those associated with a high risk of perforation or fistula formation
Has a serious active nonhealing wound/ulcer/bone fracture
Has a requirement for hemodialysis or peritoneal dialysis
Has history of human immunodeficiency virus infection
Has hepatitis B or hepatitis C virus
Has pharmacologically uncompensated, symptomatic hypothyroidism
Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

Study Design

Enrollment

904 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Belzutifan plus Zanzalintinib

Participants will receive belzutifan orally once daily (QD) PLUS zanzalintinib orally QD until one of the reasons for discontinuation of study intervention are met.

active comparator: Cabozantinib

Participants will receive cabozantinib orally QD until one of the reasons for discontinuation of study intervention are met.

Interventions

Belzutifan

Administered orally QD

Zanzalintinib

Administered orally QD

Cabozantinib

Administered orally QD

Primary outcome measure

Progression Free Survival (PFS) [ Time Frame: Up to approximately 73 months ]
Overall Survival (OS) [ Time Frame: Up to approximately 73 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839 Trialsites@msd.com

Locations

Alaska Oncology and Hematology ( Site 0133)

Recruiting

Anchorage, Alaska, United States, 99508

Contacts

Study Coordinator

907-257-9851

Providence Medical Foundation ( Site 0141)

Recruiting

Fullerton, California, United States, 92835

Contacts

Study Coordinator

714-446-5900

USC Norris Comprehensive Cancer Center ( Site 0126)

Recruiting

Los Angeles, California, United States, 90033

Contacts

Study Coordinator

800-872-2273

Cedars-Sinai Medical Center ( Site 0112)

Recruiting

Los Angeles, California, United States, 90048

Contacts

Study Coordinator

310-423-3227

New England Cancer Specialists ( Site 0132)

Recruiting

Westbrook, Maine, United States, 04092

Contacts

Study Coordinator

207-303-3300

Greater Baltimore Medical Center ( Site 0145)

Recruiting

Baltimore, Maryland, United States, 21204

Contacts

Study Coordinator

443-849-8136

Metro-Minnesota Community Clinical Oncology ( Site 0144)

Recruiting

Saint Louis Park, Minnesota, United States, 55426

Contacts

Study Coordinator

952-993-1555

Oncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 0131)

Recruiting

Omaha, Nebraska, United States, 68130-2042

Contacts

Study Coordinator

402-691-6971

Carolina Oncology Specialists, PA ( Site 9002)

Recruiting

Charlotte, North Carolina, United States, 28207

Contacts

Study Coordinator

704-342-1900

Thompson Cancer Survival Center ( Site 0125)

Recruiting

Knoxville, Tennessee, United States, 37916

Contacts

Study Coordinator

865-331-1678

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Aug 3, 2026

Last verified

Jul, 2026

Keywords

Carcinoma
Renal cell
Belzutifan
Zanzalintinib

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-08-03.