RecruitingPhase 3NCT07489495

A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)

A Phase 3, Randomized, Double-blind, Study of Belzutifan + Zanzalintinib Versus Belzutifan + Placebo in Participants With Advanced RCC Who Have Progressed on or After Both PD-1/L1 and VEGF-TKI Therapies in Sequence or in Combination (LITESPARK-034)

Sponsor

Merck Sharp & Dohme LLC

Enrollment

758 participants

Start Date

Apr 9, 2026

Study Type

INTERVENTIONAL

Conditions

Carcinoma, Renal Cell

Summary

Researchers are looking for new ways to treat advanced renal cell carcinoma (RCC). A standard (usual) treatment for certain people with RCC is belzutifan (a study medicine), which is a targeted therapy. Targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread. Researchers want to learn if adding another targeted therapy called zanzalintinib (another study medicine) can treat more people with advanced RCC than belzutifan alone. The goal of this study is to learn if people who receive belzutifan and zanzalintinib live longer overall and without the cancer getting worse compared to people who receive belzutifan and placebo.

Eligibility

Min Age: 18 Years

Inclusion Criteria3

Has a histologically confirmed diagnosis of unresectable, advanced renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features) ie, Stage IV RCC per American Joint Committee on Cancer (8th Edition)
Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
Has received no more than 3 prior systemic regimens for RCC, including only 1 prior anti-Programmed Cell Death-1/Programmed Cell Death 1 Ligand 1 therapy

Exclusion Criteria11

Has any of the following: a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or required chronic supplemental oxygen
Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
Has 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
Has current pneumonitis/interstitial lung disease
Has a history of human immunodeficiency virus infection
Has Hepatitis B or Hepatitis C virus infection
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
Has a history of solid organ transplant
Has not adequately recovered from major surgery or has ongoing surgical complications