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

RecruitingPhase 3

A Phase 3, Randomized, Open-label Study of Belzutifan + Zanzalintinib Versus Cabozantinib in Participants With Advanced RCC Who Experienced Disease Recurrence During or After Prior Adjuvant Anti-PD-1/L1 Therapy (LITESPARK-033)

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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

About the study

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.

What is being tested

Sponsor: Merck Sharp & Dohme LLC · Participants: 904 · Started: Nov 26, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT07227402

Locations in the U.S.

AlaskaAlaska Oncology and Hematology ( Site 0133), Anchorage
CaliforniaProvidence Medical Foundation ( Site 0141), Fullerton
Cedars-Sinai Medical Center ( Site 0112), Los Angeles
USC Norris Comprehensive Cancer Center ( Site 0126), Los Angeles
MaineNew England Cancer Specialists ( Site 0132), Westbrook
MarylandGreater Baltimore Medical Center ( Site 0145), Baltimore
MinnesotaMetro-Minnesota Community Clinical Oncology ( Site 0144), Saint Louis Park
NebraskaOncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 0131), Omaha
North CarolinaCarolina Oncology Specialists, PA ( Site 9002), Charlotte
TennesseeThompson Cancer Survival Center ( Site 0125), Knoxville

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.