Belzutifan for Kidney Cancer

Not currently recruiting at 3 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Anticancer antibodies

Disqualifiers: Hypoxia, Brain metastasis, Cardiac disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to ~48.5 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies a new treatment called belzutifan (also known as Welireg or MK-6482) for individuals with advanced clear cell renal cell carcinoma, a type of kidney cancer. The trial aims to determine the safety and tolerability of belzutifan at different doses. Participants will receive the treatment at varying frequencies, from once to three times a day, to identify the most effective regimen. Those who have experienced disease progression after at least one previous kidney cancer treatment might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have received certain treatments like systemic anticancer antibodies or radiotherapy shortly before starting the study. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that belzutifan is likely to be safe for humans?

Research has shown that belzutifan is generally well-tolerated by people with certain types of kidney cancer. It is approved for treating tumors in conditions like von Hippel-Lindau disease and advanced clear cell renal cell carcinoma, indicating a manageable safety profile.

Common side effects include fatigue and low levels of red blood cells, known as anemia. More serious side effects occur less frequently. This suggests that while belzutifan has some side effects, many patients manage them without major issues.

The current trial tests different doses, so side effects might vary depending on the amount taken. Overall, past research suggests that belzutifan is safe for many patients with kidney cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for kidney cancer, which typically involve surgery, immunotherapy, or tyrosine kinase inhibitors, Belzutifan is unique because it targets a specific protein known as HIF-2α. This protein plays a crucial role in allowing cancer cells to thrive in low-oxygen environments, which are common in tumors. By inhibiting HIF-2α, Belzutifan directly interferes with the cancer's ability to grow under these conditions. Researchers are excited about Belzutifan because it offers a novel mechanism of action that could potentially improve outcomes for patients who have limited options or who do not respond well to existing therapies.

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

Research has shown that belzutifan may help treat advanced clear cell renal cell carcinoma (ccRCC). Studies found that it stopped the cancer from worsening in 64% of patients and, on average, delayed the cancer's growth for about 3 months. In this trial, participants will receive different dosages of belzutifan, such as 160 mg BID, 160 mg TID, 200 mg TID, or 120 mg QD, to evaluate its effectiveness and safety. Belzutifan has also proven effective for patients when other treatments failed. Most side effects are mild, suggesting it could be a safe option for patients. ^{6 7 8 9 10}

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 clear cell renal cell carcinoma who've had disease progression after at least one systemic treatment. They must have good organ function, agree to use contraception, and not be pregnant or breastfeeding. Exclusions include those with hypoxia, other active cancers within 3 years (except certain skin/in situ cancers), HIV/hepatitis infections, prior belzutifan treatment, recent anticancer antibodies or radiotherapy, major surgery within 3 weeks, brain metastasis, severe heart/liver conditions or infections.

Inclusion Criteria

My kidney cancer cannot be surgically removed and has spread.

My organs are functioning well.

My kidney cancer has worsened after at least one treatment.

Exclusion Criteria

I have not taken any CSFs within the last 28 days.

I have been treated with belzutifan before.

I have a history of GI issues or liver problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of belzutifan as second line treatment for advanced clear cell renal cell carcinoma

Up to ~48.5 months

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 the safety and effects of different doses of Belzutifan in patients with advanced kidney cancer as a second-line treatment. It aims to understand how the body handles the drug (pharmacokinetics) and its tolerability when given after another therapy has failed.

How Is the Trial Designed?

Group I: Belzutifan 200 mg TID Experimental Treatment 1 Intervention

Participants will receive belzutifan 200 mg orally TID. Treatment will continue until progressive disease or discontinuation.

Group II: Belzutifan 160 mg TID Experimental Treatment 1 Intervention

Participants will receive belzutifan 160 mg orally three times daily (TID). Treatment will continue until progressive disease or discontinuation.

Group III: Belzutifan 160 mg BID Experimental Treatment 1 Intervention

Participants will receive belzutifan 160 mg orally twice daily (BID). Treatment will continue until progressive disease or discontinuation.

Group IV: Belzutifan 120 mg QD Experimental Treatment 1 Intervention

Participants will receive belzutifan 120 mg orally once daily (QD). Treatment will continue until progressive disease 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 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]

The combination of sorafenib, gemcitabine, and capecitabine is tolerable for patients with advanced renal cell carcinoma, with a recommended phase II dose established to minimize side effects like hand-foot syndrome.

Out of 15 patients treated, 29% showed a partial response to the therapy, and the median progression-free survival was 7.5 months, indicating potential effectiveness of this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of sorafenib plus gemcitabine and capecitabine for patients with advanced renal cell carcinoma: New York Cancer Consortium Trial NCI 6981. Tagawa, ST., Milowsky, MI., Jeske, S., et al.[2022]

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]

Novel targeted therapies, such as sunitinib, sorafenib, and temsirolimus, have significantly improved clinical outcomes for patients with metastatic clear cell renal cell cancer compared to traditional cytokine treatments.

The development of these therapies, which target the vascular endothelial growth factor and mTOR pathways, suggests a promising future for renal cancer treatment, with ongoing evaluations of combination therapies to enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy for renal cell carcinoma: a new treatment paradigm. Hutson, TE.[2020]

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]

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. merck.com merck.com/news/merck-and-eisai-announce-welireg-belzutifan-plus-lenvima-lenvatinib-met-primary-endpoint-of-progression-free-survival-pfs-in-certain-previously-treated-patients-with-advanced-renal-c/

Merck and Eisai Announce WELIREG® (belzutifan) Plus ... First treatment regimen to demonstrate a statistically significant improvement in PFS for patients whose disease progressed following anti-PD-1/L1 therapy ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39307587/

Belzutifan Efficacy and Tolerability in Patients with ... This study confirms that belzutifan can be effective and safe, even after other treatments have not worked. Keywords: Belzutifan; Clear cell; ...

4. 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 ...

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

Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau ... Belzutifan was associated with predominantly grade 1 and 2 adverse events and showed activity in patients with renal cell carcinomas and non–renal cell ...

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. 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.

8. 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 ...

9. 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 ...

10. 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 ...