758 Participants NeededMy employer runs this trial

Belzutifan + Zanzalintinib for Kidney Cancer

Recruiting at 91 trial locations
TF
Overseen ByToll Free Number
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Merck Sharp & Dohme LLC
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 explores a new treatment combination for advanced kidney cancer (renal cell carcinoma) to determine if it improves outcomes. Specifically, it tests whether adding zanzalintinib to belzutifan (a new potential drug) extends survival and slows cancer progression compared to belzutifan alone. Participants must have advanced kidney cancer and no more than three prior treatments for it. As a Phase 3 trial, this represents the final step before FDA approval, offering participants access to potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

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?

Research has shown that the combination of belzutifan and zanzalintinib is generally safe for people with kidney cancer. Studies have found that patients tolerate this combination well. Specifically, those taking belzutifan and zanzalintinib have lived longer without their cancer worsening compared to those taking cabozantinib.

Most patients experience mild side effects, which is common with cancer treatments. These findings suggest that the combination is safe for people with advanced kidney cancer, although individual experiences may vary. Potential risks should always be discussed with a healthcare provider before joining a trial.12345

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for kidney cancer, which typically involve methods like immunotherapy or chemotherapy, Belzutifan offers a unique approach by targeting the HIF-2α pathway, a key player in cancer cell survival. Researchers are excited about Belzutifan because it directly disrupts this pathway, potentially halting cancer growth more effectively. Additionally, the combination with Zanzalintinib, a tyrosine kinase inhibitor, could enhance the treatment's effectiveness by attacking the cancer cells from multiple angles, offering new hope for improved outcomes.

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 belzutifan and a placebo for treating advanced kidney cancer, known as renal cell carcinoma (RCC). Research has shown that combining belzutifan and zanzalintinib may be effective. Specifically, one study indicated that patients taking both medications lived longer and experienced better cancer control compared to those on other treatments. The combination achieved a 70% response rate, with many patients seeing their tumors shrink or stop growing. Patients also experienced longer periods without their cancer worsening. These results suggest that adding zanzalintinib to belzutifan could offer a more effective treatment option for advanced RCC.12467

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 can't be removed by surgery. Participants must have a certain type of RCC, measurable tumors, and can have had up to three previous treatments for their cancer.

Inclusion Criteria

I have advanced kidney cancer that cannot be removed by surgery.
I have tumors that can be measured by scans or tests.
I have had 3 or fewer treatments for kidney cancer, with only one anti-PD-1/PD-L1 therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 120 mg belzutifan orally and either 60 mg zanzalintinib or placebo once daily

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

Up to 50 months

What Are the Treatments Tested in This Trial?

Interventions

  • Belzutifan
  • Placebo
  • Zanzalintinib

Trial Overview

The study compares two groups: one gets belzutifan plus zanzalintinib (both targeted therapies), and the other gets belzutifan plus a placebo. The goal is to see if adding zanzalintinib helps people live longer or delays cancer worsening.

How Is the Trial Designed?

2

Treatment groups

Experimental Treatment

Active Control

Group I: Belzutifan + ZanzalintinibExperimental Treatment2 Interventions
Group II: Belzutifan + PlaceboActive Control2 Interventions

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

The efficacy and safety of belzutifan inhibitor in patients ... - PMC

exhibited good safety and efficacy in clinical trials. has only a 12% five-year survival rate, ORR of 70%, 98% and an mPFS time of 30.3 months

NCT07227402 | A Clinical Study of Belzutifan and ...

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

Belzutifan + Zanzalintinib for Kidney Cancer

Patients who received belzutifan responded better, with 22% showing improvement compared to only 3.5% with other treatments. It also delayed disease ...

Belzutifan plus cabozantinib as first-line treatment for ...

35 (70%) of 50 patients had a confirmed objective response, and 49 (98%) of 50 patients had a best overall response of stable disease or better.

Belzutifan in 2026: Phase 3 Trials, Approvals & Surprises

Two positive LITESPARK trials signal new FDA approvals for belzutifan in kidney cancer—while one frontline triplet fails.

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

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

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

demonstrated superior progression-free survival and objective response rate for belzutifan