Drug Combinations for Kidney Cancer

Recruiting in Palo Alto (17 mi)

+276 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Merck Sharp & Dohme Corp.

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The goal of this study is to evaluate the efficacy and safety of pembrolizumab plus belzutifan plus lenvatinib or pembrolizumab/quavonlimab plus lenvatinib versus pembrolizumab plus lenvatinib as first-line treatment in participants with advanced clear cell renal cell carcinoma (ccRCC). The primary hypotheses are (1) pembrolizumab plus belzutifan plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to progression-free survival (PFS) and overall survival (OS), in advanced ccRCC participants; and (2) pembrolizumab/quavonlimab plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to PFS and OS, in advanced ccRCC participants.

Eligibility Criteria

This trial is for adults with advanced clear cell renal cell carcinoma who haven't had systemic therapy for it. They must have good organ function, controlled blood pressure, and agree to contraception if applicable. Exclusions include other active cancers within 3 years, recent major surgery or radiotherapy, certain heart diseases, lung conditions like interstitial disease or pneumonitis, uncontrolled infections including HIV or Hepatitis B.

Inclusion Criteria

I started treatment for bone loss at least 2 weeks before joining the study.

My blood pressure is under control, with or without medication.

My organs are functioning well.

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Exclusion Criteria

I have had or currently have lung inflammation treated with steroids.

I have a history of Hepatitis B.

I have not had major surgery within the last 4 weeks, except for kidney removal.

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Treatment Details

Interventions

Belzutifan (Small Molecule)
Lenvatinib (Small Molecule)
Pembrolizumab (Monoclonal Antibodies)
Pembrolizumab/Quavonlimab (Monoclonal Antibodies)

Trial OverviewThe study tests the effectiveness of pembrolizumab combined with belzutifan and lenvatinib or a combo of pembrolizumab/quavonlimab with lenvatinib against just pembrolizumab plus lenvatinib in treating kidney cancer. It aims to see which combination leads to longer survival without disease progression.

Participant Groups

3Treatment groups

Experimental Treatment

Active Control

Group I: Pembrolizumab/Quavonlimab + LenvatinibExperimental Treatment2 Interventions

Participants will receive pembrolizumab/quavonlimab (co-formulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered IV Q6W for up to 18 administrations (up to \~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.

Group II: Pembrolizumab + Belzutifan + LenvatinibExperimental Treatment3 Interventions

Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 18 administrations (up to \~2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation.

Group III: Pembrolizumab + LenvatinibActive Control2 Interventions

Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 18 administrations (up to \~2 years). Lenvatinib will be administered orally QD 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