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Belzutifan and Zanzalintinib Combination for Advanced Renal Cell Carcinoma Treatment

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Study Aim

This phase 3 study aims to evaluate the effectiveness of Belzutifan and Zanzalintinib combination in improving overall survival and delaying disease progression in individuals with advanced renal cell carcinoma.

What is being tested

Belzutifan

+ Placebo

+ Zanzalintinib

Drug
Who is being recruted

Urogenital Diseases+13

+ Adenocarcinoma

+ Carcinoma

Over 18 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 3
Interventional
Study Start: April 2026
See protocol details

Summary

Principal SponsorMerck Sharp & Dohme LLC
Last updated: March 25, 2026
Sourced from a government-validated database.Claim as a partner

Study start date: April 17, 2026

Actual date on which the first participant was enrolled.

This study focuses on finding better treatment options for advanced renal cell carcinoma (RCC), a type of kidney cancer. Currently, a standard treatment for certain RCC patients is belzutifan, a targeted therapy that helps control how specific cancer cells grow and spread. The researchers aim to discover if combining belzutifan with another targeted therapy, zanzalintinib, can treat more advanced RCC patients effectively than using belzutifan alone. The potential outcomes of this study could significantly improve care for those with advanced RCC and address current challenges in treatment. During this trial, participants receive either a combination of belzutifan and zanzalintinib or belzutifan and a placebo. The primary goals are to evaluate if patients receiving the combination treatment live longer overall and experience a longer period without their cancer worsening, compared to those receiving belzutifan and a placebo. The study measures these outcomes by tracking the time from randomization to death due to any cause and the time from randomization to the first documented disease progression or death, based on specific evaluation criteria (RECIST 1.1) through blinded independent central review.

Official TitleA 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)
NCT07489495
Principal SponsorMerck Sharp & Dohme LLC
Last updated: March 25, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details

758 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.



Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Any sex

Biological sex of participants that are eligible to enroll.

Over 18 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Urogenital DiseasesAdenocarcinomaCarcinomaCarcinoma, Renal CellFemale Urogenital Diseases and Pregnancy ComplicationsKidney DiseasesKidney NeoplasmsNeoplasmsNeoplasms by Histologic TypeNeoplasms by SiteNeoplasms, Glandular and EpithelialUrogenital NeoplasmsUrologic DiseasesUrologic NeoplasmsFemale Urogenital DiseasesMale Urogenital Diseases

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

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives

2 intervention groups are designated in this study

This study does not include a placebo group 

Treatment Groups

Group I

Active Comparator
Participants will receive 120 mg belzutifan orally and zanzalintinib-matching placebo once daily for approximately 24 months.

Group II

Experimental
Participants will receive 120 mg belzutifan orally and 60 mg zanzalintinib once daily for approximately 24 months.

Study Objectives

Primary Objectives

Secondary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
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Recruiting soonNo study centers