Belzutifan for Kidney Cancer

Not currently recruiting at 57 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must be taking: Anti-PD-1/L1 therapy

Must not be taking: CYP3A4 inducers

Disqualifiers: Hypoxia, CNS metastases, Cardiac disease, Hepatic impairment, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 27 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called belzutifan for individuals with advanced kidney cancer that includes a clear cell component and has progressed after previous treatment. Researchers aim to determine if a higher dose of belzutifan is more effective than the standard dose in shrinking tumors. The trial includes two groups: one receiving 120 mg and the other 200 mg of belzutifan daily. Individuals whose kidney cancer has worsened after specific therapies and who can provide a tumor sample might be suitable for this study. As a Phase 2 trial, this research measures how well belzutifan works in an initial, smaller group, offering participants a chance to contribute to important findings.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take certain medications like strong or moderate inducers of CYP3A4 during the study.

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

Research has shown that belzutifan is approved for treating certain cancers, such as von Hippel-Lindau disease and advanced kidney cancer. This approval indicates some evidence of its safety for humans.

Studies have found that belzutifan is generally well-tolerated, with common side effects including tiredness, dizziness, and anemia (a low red blood cell count). Most people can manage these side effects.

Safety data from earlier trials for similar conditions suggest that both doses of belzutifan in this study are expected to be similarly safe. However, the higher dose might have a greater chance of causing side effects, which is important to consider when deciding to join the trial.

Belzutifan's use in other approved conditions supports its safety, but individual experiences can vary. Participants should discuss any concerns with their healthcare provider before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for kidney cancer?

Most treatments for kidney cancer, like sunitinib or pazopanib, are tyrosine kinase inhibitors that target specific proteins to slow cancer growth. But belzutifan works differently, targeting a protein known as HIF-2α, which plays a crucial role in cancer cell survival under low oxygen conditions. This unique mechanism could offer new hope, especially for patients who have not responded well to current therapies. Researchers are particularly excited because belzutifan is administered orally and may provide a more convenient treatment option with potentially fewer side effects.

What evidence suggests that belzutifan might be an effective treatment for kidney cancer?

Research has shown that belzutifan yields promising results for treating advanced kidney cancer. In patients with VHL disease–associated kidney cancer, nearly half experienced tumor shrinkage when treated with belzutifan. Other studies have found that combinations using belzutifan helped patients live longer without their cancer worsening. The disease control rate was 64%, indicating that many patients saw their cancer either remain stable or shrink. This trial will evaluate two different dosages of belzutifan, 120 mg and 200 mg, to determine its effectiveness in managing kidney cancer. These findings suggest belzutifan could effectively manage kidney cancer. ^{4 6 7 8 9}

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 adults with advanced renal cell carcinoma who have previously been treated with anti-PD-1/L1 therapy. They must be in good physical condition (KPS score ≥70%), able to use contraception, and not pregnant or breastfeeding. Participants should have no more than three prior treatments for RCC, only one of which can be anti-PD-1/L1 therapy.

Inclusion Criteria

You have a condition that can be measured using specific medical guidelines.

I have had 3 or fewer treatments for advanced kidney cancer.

I am not pregnant or breastfeeding and either cannot become pregnant or agree to use birth control during and after the study.

Exclusion Criteria

I haven't had cancer treatment with antibodies in the last 4 weeks.

I have been treated with belzutifan or a similar drug before.

Is currently participating in a study of an investigational agent or is currently using an investigational device

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 120 mg or 200 mg of belzutifan daily until disease progression or discontinuation

Up to approximately 27 months

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belzutifan

Trial Overview

The study tests two different doses of belzutifan to see which one works better for treating advanced renal cell carcinoma after previous therapies. The main goal is to compare the objective response rates between the standard dose and a higher dose.

How Is the Trial Designed?

Group I: Belzutifan 200 mg Experimental Treatment 1 Intervention

Participants receive 200 mg of belzutifan by oral administration, once a day (QD), until disease progression or discontinuation.

Group II: Belzutifan 120 mg Experimental Treatment 1 Intervention

Participants receive 120 mg of belzutifan by oral administration, QD, until disease progression or discontinuation.

Belzutifan is already approved in United States for the following indications:

Approved in United States as Welireg for:

• Advanced renal cell carcinoma (RCC) following a PD-1 or PD-L1 inhibitor and a VEGF TKI
• Von Hippel-Lindau disease-associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

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

Published Research Related to This Trial

The HIF-2α inhibitor, belzutifan, has shown effectiveness in treating advanced clear-cell renal cell carcinoma in the LITESPARK-005 and -003 trials, both as a standalone treatment and in combination with VEGFR tyrosine kinase inhibitors.

These promising results suggest that belzutifan could be used more broadly in cancer treatment, potentially extending its application beyond just von Hippel-Lindau disease-associated cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding "Practice-Changing" Belzutifan's Reach in RCC. [2023]

Belzutifan, a first-in-class HIF-2α inhibitor, shows promising antitumor activity in patients with clear cell renal cell carcinoma (RCC) who have previously been treated, indicating its potential as a new treatment option.

The ongoing phase III study is comparing the combination of belzutifan with lenvatinib against cabozantinib in patients with advanced RCC who have progressed after anti-PD-1/PD-L1 therapy, addressing a significant need for effective treatments in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy. Motzer, RJ., Schmidinger, M., Eto, M., et al.[2023]

In a phase 1 study involving 98 patients with advanced solid tumors and clear cell renal cell carcinoma (ccRCC), belzutifan (MK-6482) was found to be well tolerated, with no dose-limiting toxicities at doses up to 160 mg, establishing a recommended phase 2 dose of 120 mg once daily.

Belzutifan demonstrated preliminary anti-tumor activity in ccRCC, with a 25% objective response rate and a median progression-free survival of 14.5 months, indicating its potential as an effective treatment option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Choueiri, TK., Bauer, TM., Papadopoulos, KP., et al.[2022]

The combination of belzutifan and cabozantinib shows promising antitumor activity in patients with advanced clear cell renal cell carcinoma who have already undergone previous treatments.

This study highlights the potential of this drug combination as a new therapeutic option for patients with this challenging form of kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belzutifan Plus Cabozantinib Is Effective in Immunotherapy-Treated Renal Cell Carcinoma. [2023]

Belzutifan (Welireg™) is an oral medication that inhibits HIF-2α and has been approved in the USA for treating patients with von Hippel-Lindau (VHL) disease who have associated renal cell carcinoma (RCC) and other tumors, marking a significant advancement in targeted cancer therapy.

Clinical studies are ongoing to evaluate the efficacy of belzutifan in treating other solid tumors, including clear cell renal cell carcinoma (ccRCC) and pancreatic neuroendocrine tumors (pNET), indicating its potential for broader applications in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belzutifan: First Approval. Deeks, ED.[2022]

In a phase 2 study involving 52 patients with advanced clear cell renal cell carcinoma who had previously received immunotherapy, the combination of belzutifan and cabozantinib showed promising antitumour activity, with 30.8% of patients achieving a confirmed objective response, including one complete response.

The treatment was associated with manageable safety concerns, primarily hypertension (27% of patients), and serious treatment-related adverse events occurred in 29% of patients, indicating that while the combination therapy is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study. Choueiri, TK., McDermott, DF., Merchan, J., et al.[2023]

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.

eisai.com

eisai.com/news/2025/news202575.html

Merck & Co., Inc., Rahway, NJ, USA and ...

Real-World Treatment Patterns and Clinical Outcomes Among Patients With Advanced Renal Cell Carcinoma. Clinical Genitourinary Cancer April 2024, ...

3.

welireghcp.com

welireghcp.com/von-hippel-lindau/efficacy/

Efficacy Data for WELIREG® (belzutifan) | VHL Disease

Nearly half of patients achieved tumor reduction in VHL disease–associated RCC with WELIREG · MEDIAN DURATION OF RESPONSE WAS NOT REACHED · NCCN Clinical Practice ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04489771

NCT04489771 | A Study of Belzutifan (MK-6482) in ...

This study will compare the efficacy and safety of two doses of belzutifan in participants with advanced renal cell carcinoma (RCC) with clear cell ...

5.

onclive.com

onclive.com/view/belzutifan-based-combinations-meet-dfs-pfs-end-points-in-renal-cell-carcinoma

Belzutifan-Based Combinations Meet DFS, PFS End Points ...

LITESPARK-011 and LITESPARK-022 trials showed significant PFS and DFS improvements in RCC with belzutifan combinations, surpassing cabozantinib ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12483163/

The safety profile of belzutifan in renal tumors - PubMed Central

Belzutifan is a HIF-2ɑ inhibitor approved for the treatment of tumors in von Hippel-Lindau (VHL) syndrome and sporadic metastatic clear cell ...

7.

ema.europa.eu

ema.europa.eu/en/medicines/human/EPAR/welireg

Welireg | European Medicines Agency (EMA)

Welireg is a cancer medicine used to treat: adults with advanced clear cell renal cell carcinoma (a type of kidney cancer) that has worsened ...

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2024/215383Orig1s007lbl.pdf

WELIREG® (belzutifan) tablets, for oral use - accessdata.fda.gov

The safety of WELIREG was evaluated in an open-label clinical ... kidney cancer called renal cell carcinoma. (RCC), tumors in the brain ...

9.

urologytimes.com

urologytimes.com/view/eric-jonasch-md-shares-pooled-safety-data-on-belzutifan-in-advanced-rcc

Eric Jonasch, MD, shares pooled safety data on belzutifan ...

Belzutifan, a HIF-2α inhibitor, is approved for von Hippel-Lindau disease and advanced renal cell carcinoma, with a focus on its safety profile.