Belzutifan + Zanzalintinib for Kidney Cancer

Recruiting at 19 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Bone resorptive therapy

Must not be taking: CYP3A4 inhibitors, Anticoagulants

Disqualifiers: Cardiovascular disease, CNS metastases, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with clear cell renal cell carcinoma (ccRCC). The research aims to determine if a combination of two experimental drugs, Belzutifan and Zanzalintinib, is safe and effective for those whose cancer returned during or after a specific therapy. The trial consists of two parts: one to assess safety and another to evaluate treatment efficacy. It targets individuals whose ccRCC returned during or within two years after a particular cancer therapy and who can take oral medication. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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

The trial requires that you stop taking strong inhibitors of cytochrome P450 3A4 (a liver enzyme) and anticoagulants or platelet inhibitors for the duration of the study. If you are on these medications, you will need to discuss with your doctor about stopping them.

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

Previous studies have shown that belzutifan generally has a manageable safety profile. Most side effects were mild to moderate, and only about 6% of patients stopped treatment due to them. Common issues included mild anemia, a condition characterized by insufficient healthy red blood cells. However, some individuals experienced more serious anemia.

Belzutifan has already received approval for certain types of tumors, indicating it is generally well-tolerated.

Specific safety data for zanzalintinib is not yet available, as it is being tested with other treatments. Researchers are still collecting safety information. The trial under consideration is in its early stages, so the safety of the treatment in humans is still being evaluated. This trial will help determine if these treatments are safe when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments Belzutifan and Zanzalintinib for kidney cancer because they introduce innovative ways to tackle the disease. Unlike standard treatments that often target specific proteins or pathways, Belzutifan works by inhibiting hypoxia-inducible factor 2-alpha (HIF-2α), a protein that plays a key role in tumor growth and survival under low-oxygen conditions. This approach could offer a new angle for slowing cancer progression. Meanwhile, Zanzalintinib is a next-generation tyrosine kinase inhibitor that might provide more precise targeting with potentially fewer side effects. Together, these treatments promise a fresh strategy that could enhance effectiveness and tolerability compared to current options.

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

Studies have shown promising results for belzutifan in treating kidney cancer. Patients who received belzutifan responded better, with 22% showing improvement compared to only 3.5% with other treatments. It also delayed disease progression, with 64% of patients experiencing stable disease. In this trial, some participants will receive belzutifan alone.

For the combination of belzutifan and zanzalintinib, another treatment arm in this trial, early findings are encouraging for kidney cancer treatment. A recent kidney cancer symposium highlighted the promise of this combination, though more research is needed to confirm its effectiveness. Together, these treatments offer hope for better outcomes in managing kidney cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for individuals with clear cell renal cell carcinoma (ccRCC) who have seen their cancer return during or after treatment with anti-PD-(L)1 therapy. Specific details about inclusion and exclusion criteria are not provided, but typically participants must meet certain health standards and may be excluded based on previous treatments or health conditions.

Inclusion Criteria

Has measurable disease per RECIST 1.1 as assessed by investigator and verified by BICR

Is able to swallow oral medication

A participant assigned female sex at birth is not breast feeding at least 96 days after the last dose of study intervention. A participant of childbearing potential (POCBP) is not pregnant and has a negative highly sensitive pregnancy test before the first dose of study intervention. A POCBP uses a highly effective contraceptive method, and continues using contraception at least 30 days after the last dose of Belzutifan, and at least 186 days after the last dose of Zanzalintinib

Exclusion Criteria

I haven't had major surgery or serious injuries in the last 8 weeks.

My scans show my tumor is affecting major blood vessels or has hollow areas.

I have been treated for an autoimmune disease in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Demonstrate a tolerable safety profile for the combination of investigational agents

3 weeks

Efficacy

Evaluate the safety and efficacy of experimental combinations of investigational agents

Up to approximately 74 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belzutifan
• Zanzalintinib

Trial Overview The study is testing the safety and effectiveness of combining two experimental drugs, Belzutifan and Zanzalintinib, in treating ccRCC. It includes a preliminary phase to ensure safety followed by a phase focused on how well the drug combination works.

How Is the Trial Designed?

Group I: Zanzalintinib at Dose Level 1 or 2 + Belzutifan Experimental Treatment 2 Interventions

Participants will be allocated to receive zanzalintinib at dose level 1 or 2 + belzutifan daily until progressive disease or discontinuation

Group II: Belzutifan Experimental Treatment 1 Intervention

Participants will receive belzutifan daily until progressive disease or discontinuation

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

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

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

Exelixis

Chief Executive Officer since 2010

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

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12509838/

59: Real-World efficacy and safety of belzutifan in sporadic ... The disease control rate was 64%. The median OS was 6.93 months (95% CI: 3.75-12.58). The median PFS was 3.09 months (95% CI 2.53-5.72). AEs of ...

2. dana-farber.org dana-farber.org/newsroom/news-releases/2023/kidney-cancer-study-shows-improved-outcomes-for-patients-with-advanced-disease-when-treated-with-belzutifan-over-everolimus

Kidney cancer study shows improved outcomes for patients ... The overall response rate was also higher with belzutifan, at 22% versus 3.5%, and 13 patients experienced a complete response with belzutifan ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2103425

Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau ... A total of 54 patients (89%) continued to receive treatment with belzutifan as of the data cutoff date. A total of 30 patients had confirmed ...

4. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.70023

Belzutifan's role in the treatment landscape of clear cell renal ... The major efficacy outcome measures were progression-free survival (PFS) and OS. Significant improvement in PFS was demonstrated for belzutifan ...

5. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-kidney-cancer/158328-asco-gu-2025-exploring-the-efficacy-of-belzutifan-in-the-treatment-of-renal-cell-carcinoma-associated-with-von-hippel-lindau-disease-a-comparative-analysis-with-external-control-arm.html

ASCO GU 2025: Exploring the Efficacy of Belzutifan in ... The results support the demonstrated antitumor activity and efficacy of belzutifan in the treatment of VHL-RCC seen in LS-004. Presented by: ...

6. academic.oup.com academic.oup.com/oncolo/advance-article/doi/10.1093/oncolo/oyaf274/8249253?searchresult=1

The safety profile of belzutifan in renal tumors: real-world data ... While low-grade anemia remained common (82.8%), higher rates of grade ≥ 3 anemia and grade ≥ 3 hypoxia were observed in spRCC patients in LITESPARK-005,11 ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e16531

Safety and efficacy profile of belzutifan, a hypoxia-inducible ... Pooled proportion of patients experiencing any grade AE and grade ≥3 AE was 98% (95% CI: 95% – 99%) and 49% (95% CI: 29% – 69%) respectively.

8. urotoday.com urotoday.com/conference-highlights/suo-2024/suo-2024-kidney-cancer/156697-suo-2024-in-depth-characterization-of-the-safety-profile-of-belzutifan-monotherapy-in-patients-with-renal-cell-carcinoma-a-pooled-analysis-of-four-clinical-trials.html

In-Depth Characterization of the Safety Profile of Belzutifan ... .Belzutifan demonstrated a generally manageable safety profile, with few patients discontinuing treatment due to AEs (6%) in a pooled analysis ...