Belzutifan vs Everolimus for Renal Cell Carcinoma

Recruiting at 172 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

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

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 78 months

755 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically strong or moderate inhibitors and inducers of CYP3A4, for the duration of the study. If you are on these medications, you will need to discuss with your doctor about discontinuing them before participating.

What data supports the effectiveness of the drug Everolimus for treating renal cell carcinoma?

Everolimus has been shown to increase progression-free survival in patients with advanced renal cell carcinoma, particularly after other treatments like sunitinib and sorafenib have failed. In clinical trials, patients taking Everolimus had a median progression-free survival of 4.9 months compared to 1.9 months for those on a placebo. ^{1 2 3 4 5}

What is the safety profile of Everolimus for renal cell carcinoma?

Everolimus, also known as Afinitor, is generally well tolerated in patients with advanced renal cell carcinoma, with most side effects being mild to moderate. Common serious side effects include mouth sores, fatigue, lung inflammation, and infections. ^{1 3 4 5 6}

What makes the drugs Belzutifan and Everolimus unique for treating renal cell carcinoma?

Belzutifan and Everolimus are unique because they target specific pathways involved in cancer growth. Everolimus is an mTOR inhibitor, which helps slow down cancer cell growth, while Belzutifan is a newer drug that targets a different pathway, potentially offering a novel approach for patients who have not responded to other treatments. ^{1 3 4 5 7}

What is the purpose of this trial?

The primary objective of this study is to compare belzutifan to everolimus with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) and to compare everolimus with respect to overall survival (OS). The hypothesis is that belzutifan is superior to everolimus with respect to PFS and OS.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced renal cell carcinoma who've had no more than three prior treatments, are not pregnant or breastfeeding, and agree to use contraception. They must have progressed after treatment with specific cancer drugs (PD-1/L1 inhibitors and VEGF-TKIs) and have good organ function. Exclusions include other active cancers within 3 years, brain metastases, significant heart issues, allergies to the study drugs, recent major surgery or certain medications.

Inclusion Criteria

I am not pregnant or breastfeeding and, if able to have children, I agree to use contraception as advised.

My kidney cancer worsened after treatment with PD-1/L1 and VEGF-TKI.

My kidney cancer cannot be surgically removed and has spread.

Exclusion Criteria

I cannot take pills by mouth or have a condition that affects how my body absorbs medication.

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

I have not had major surgery in the last 3 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-In

Non-randomized participants received up to 120 mg of belzutifan QD

Not specified

Treatment

Randomized participants received either 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or discontinuation

Up to approximately 78 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 49 months

Treatment Details

Interventions

• Belzutifan
• Everolimus

Trial Overview The study aims to see if Belzutifan improves survival without cancer progression compared to Everolimus in patients with advanced kidney cancer. It's a head-to-head comparison of these two drugs' effectiveness over time.

Participant Groups

Group I: Safety Run-In Experimental Treatment 1 Intervention

Non-Randomized participants enrolled into the Safety Run-in received up to 120 mg of belzutifan QD.

Group II: Belzutifan Experimental Treatment 1 Intervention

Randomized participants received 120 mg of belzutifan orally once daily (QD), until disease progression or discontinuation.

Group III: Everolimus Active Control 1 Intervention

Randomized participants received 10 mg of Everolimus orally 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

Everolimus, an oral mTOR inhibitor, significantly improves progression-free survival in patients with clear cell renal cancer, increasing it from a median of 1.9 months to 4.9 months in a phase III trial with a hazard ratio of 0.33 (P < 0.001).

The treatment is generally well-tolerated, with mild to moderate side effects that can be managed, and it has been approved as a validated option for patients who have progressed on VEGFR inhibitors, with ongoing trials exploring its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus: the first approved product for patients with advanced renal cell cancer after sunitinib and/or sorafenib. Coppin, C.[2021]

References

1. Belgium pubmed.ncbi.nlm.nih.gov

[Everolimus (RAD001/Afinitor) in the treatment of metastatic cell carcinoma]. [2021]

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

A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer. [2021]

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

Everolimus: the first approved product for patients with advanced renal cell cancer after sunitinib and/or sorafenib. [2021]

4. Spain pubmed.ncbi.nlm.nih.gov

Everolimus in renal cell carcinoma. [2021]

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

Everolimus - a new approach in the treatment of renal cell carcinoma. [2021]

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

Everolimus: a new mammalian target of rapamycin inhibitor for the treatment of advanced renal cell carcinoma. [2021]

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

Randomized Open-Label Phase II Trial of Apitolisib (GDC-0980), a Novel Inhibitor of the PI3K/Mammalian Target of Rapamycin Pathway, Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma. [2022]