904 Participants NeededMy employer runs this trial

Belzutifan + Zanzalintinib for Kidney Cancer

(LITESPARK-033 Trial)

Recruiting at 129 trial locations
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Overseen ByToll Free Number
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of two drugs, belzutifan and zanzalintinib, can treat advanced kidney cancer more effectively than the current treatment, cabozantinib. Researchers seek to find out if this new treatment can extend patients' lives and prevent cancer progression. The trial targets individuals with advanced kidney cancer that has recurred after specific therapies. As a Phase 3 trial, it represents the final step before FDA approval, providing patients an opportunity to access potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Recent studies have shown that belzutifan is generally well-tolerated by patients. Common side effects include fatigue and dizziness, typically mild. Some patients experienced more serious side effects, such as low oxygen levels in the blood, but these were less common.

Early reports on zanzalintinib indicate a safety profile similar to other treatments in its category. Common side effects include nausea and diarrhea, with some patients experiencing increased blood pressure.

As this trial is in a later phase, researchers have already gathered substantial safety data. This data suggests that the combination of belzutifan and zanzalintinib is reasonably safe for further study. However, new side effects may still emerge, so all participants are closely monitored.

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for kidney cancer because they offer new ways to tackle the disease. Belzutifan, combined with Zanzalintinib, targets a novel pathway in cancer cells, potentially improving outcomes by starving tumors of oxygen. Unlike traditional treatments like sunitinib or pazopanib, which focus on blocking blood vessel growth, this combination aims to directly disrupt tumor metabolism. Meanwhile, Cabozantinib, the comparator, is already known for its effectiveness in targeting specific cancer growth pathways, but the new combination could provide an even more effective approach. These advancements could lead to more effective and targeted treatment options for patients with kidney cancer.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

This trial will compare the combination of belzutifan and zanzalintinib with cabozantinib for treating advanced kidney cancer. Research has shown that using belzutifan and zanzalintinib together may help treat this condition. One study found that patients taking this combination experienced longer periods of stable cancer and better treatment responses compared to those taking cabozantinib. Additionally, belzutifan alone improved conditions in 22% of kidney cancer patients. When zanzalintinib was combined with another drug, it showed a 63% response rate in advanced kidney cancer cases. These findings suggest that belzutifan and zanzalintinib together could effectively treat recurrent advanced kidney cancer.12345

Who Is on the Research Team?

MD

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with advanced kidney cancer (renal cell carcinoma) that has come back after or during treatment with certain immunotherapies. Participants must not have had other treatments for their advanced cancer and need to have measurable disease.

Inclusion Criteria

I have advanced, inoperable kidney cancer with clear cell features.
My cancer can be measured on scans or tests.
My cancer came back during or within 24 months after anti-PD-1/L1 therapy.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belzutifan and zanzalintinib or cabozantinib until disease progression or unacceptable toxicity

Up to approximately 73 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 25 months

What Are the Treatments Tested in This Trial?

Interventions

  • Belzutifan
  • Cabozantinib
  • Zanzalintinib

Trial Overview

The study compares two treatments: one group gets belzutifan plus zanzalintinib, while the other receives cabozantinib alone. The goal is to see which approach helps people live longer and keeps the cancer from getting worse.

How Is the Trial Designed?

2

Treatment groups

Experimental Treatment

Active Control

Group I: Belzutifan plus ZanzalintinibExperimental Treatment2 Interventions
Group II: CabozantinibActive Control1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials
4,096
Recruited
5,232,000+
Chirfi Guindo profile image

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis profile image

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Exelixis

Industry Sponsor

Trials
126
Recruited
20,500+
Michael M. Morrissey profile image

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman profile image

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Citations

ASCO 2026: LITESPARK-033: Phase 3 Study of Belzutifan ...

Notably, the phase III LITESPARK-011 trial previously demonstrated superior progression-free survival and objective response rate for belzutifan ...

A Clinical Study of Belzutifan and Zanzalintinib in People ...

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

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39307587/

Belzutifan Efficacy and Tolerability in Patients with ...

The median OS was 14.72 mo (95% CI 7.34-22.10). Of 22 patients, four (18.2%) patients required dose reductions and three (13.6%) patients ...

Belzutifan and Zanzalintinib Combination for Advanced ...

This phase 3 study aims to evaluate the effectiveness of Belzutifan and Zanzalintinib combination in improving overall survival and delaying disease ...

Belzutifan + Zanzalintinib for Kidney Cancer

Studies have shown promising results for belzutifan in treating kidney cancer. Patients who received belzutifan responded better, with 22% showing improvement ...