Belzutifan for Kidney Cancer

Recruiting at 48 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

154 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will compare the efficacy and safety of two doses of belzutifan in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy. The primary hypothesis is that the higher dose of belzutifan is superior to the standard dose in terms of objective response rate (ORR).

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.

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

Research shows that Belzutifan, when combined with other drugs like cabozantinib or lenvatinib, has shown promising results in treating advanced kidney cancer, especially in patients who have already received other treatments. It has demonstrated antitumor activity, meaning it can help shrink or slow the growth of tumors in these patients. ^{1 2 3 4 5}

How is the drug Belzutifan unique for treating kidney cancer?

Belzutifan is unique because it is an oral drug that specifically 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 5 6 7}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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 (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]

References

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

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

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

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

4. 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]

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

Belzutifan: First Approval. [2022]

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

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

7. 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]