Belzutifan for Kidney Cancer

Recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Must not be taking: HIF-2α inhibitors, Anti-VEGF

Disqualifiers: Metastatic disease, Prior belzutifan, 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: 12

Duration: Minimum of 3 years

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study is designed to investigate belzutifan as a treatment for VHL disease associated RCC.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had any prior systemic anti-cancer therapy.

How is the drug Belzutifan unique for treating kidney cancer?

Belzutifan is unique because it is an oral drug that specifically targets and inhibits hypoxia-inducible factor-2α (HIF-2α), a protein that often accumulates in kidney cancer cells and promotes tumor growth. This mechanism is different from other treatments, making it a novel option for patients with clear cell renal cell carcinoma. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Belzutifan for kidney cancer?

Belzutifan has shown promising results in treating advanced kidney cancer, especially when combined with other drugs like cabozantinib or lenvatinib, in patients who have already received other treatments. It works by targeting a specific protein (HIF-2α) involved in cancer growth, and studies suggest it can help control the disease in these patients. ^{1 3 5 6 7}

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 von Hippel Lindau disease who have at least one measurable kidney cancer tumor but don't need immediate surgery. They shouldn't have used belzutifan or similar drugs before, had any cancer treatments like anti-VEGF therapy, require urgent tumor surgery, or have metastatic disease.

Inclusion Criteria

I have a measurable kidney cancer tumor that doesn't need immediate surgery.

I have been diagnosed with von Hippel Lindau disease.

Exclusion Criteria

My scans show cancer has spread to other parts of my body.

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

I have received treatments targeting cancer growth.

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 once daily. Treatment is continuous with radiological evaluations approximately every 12 weeks.

Minimum of 3 years

Radiological evaluations every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with evaluations every 24 weeks or more frequently if clinically indicated.

Up to approximately 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Belzutifan

Trial Overview The study tests belzutifan as a potential treatment for kidney cancer associated with von Hippel Lindau disease. It aims to understand the effectiveness and safety of this medication in patients diagnosed with VHL-related renal cell carcinoma.

How Is the Trial Designed?

Group I: Open Label Belzutifan Experimental Treatment 1 Intervention

Participants receive 120 mg belzutifan orally once daily. Participants may continue to receive belzutifan in the absence of unacceptable treatment related toxicity or unequivocal disease progression.

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?

Peloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Lead Sponsor

Trials

8

Recruited

460+

Peloton Therapeutics, Inc.

Lead Sponsor

Trials

8

Recruited

460+

Published Research Related to This Trial

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]

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]

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]

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 (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 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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

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

2. England 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. New Zealand pubmed.ncbi.nlm.nih.gov

Belzutifan: First Approval. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Belzutifan (MK-6482): Biology and Clinical Development in Solid Tumors. [2023]