Immune and Targeted Combination Therapies for Kidney Cancer

Recruiting in Palo Alto (17 mi)

+55 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Merck Sharp & Dohme LLC

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Substudy 03A is part of a larger research study that is testing experimental treatments for renal cell carcinoma (RCC). The larger study is the umbrella study (U03). The goal of substudy 03A is to evaluate the safety and efficacy of experimental combinations of investigational agents in participants with advanced first line (1L) clear cell renal cell carcinoma (ccRCC). This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to demonstrate a tolerable safety profile for the combination of investigational agents. There will be no hypothesis testing in this study.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced first line clear cell renal cell carcinoma who haven't had systemic therapy for it. They must be able to take oral meds, have good organ function, and manage contraception if needed. Excluded are those with recent vaccines, multiple cancer treatments, immunodeficiency or other cancers within 3 years.

Inclusion Criteria

My organs are functioning well.

Side effects from my last treatment are mild or gone.

My kidney cancer has spread and is confirmed by tissue analysis.

See 6 more

Exclusion Criteria

I have received an organ or tissue transplant from another person.

I have had serious heart problems in the last year.

You have been diagnosed with HIV.

See 15 more

Treatment Details

Interventions

Belzutifan (Other)
Favezelimab (Other)
Lenvatinib (Other)
Pembrolizumab (Checkpoint Inhibitor)
Quavonlimab (Other)
Vibostolimab (Other)

Trial OverviewThe study tests combinations of experimental drugs like Pembrolizumab and others (Favezelimab/Pembrolizumab, Belzutifan) in two phases: a safety phase to ensure tolerability and an efficacy phase without hypothesis testing.

Participant Groups

5Treatment groups

Experimental Treatment

Group I: Pembrolizumab + LenvatinibExperimental Treatment2 Interventions

Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 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 IV Q6W for up to 17 administrations (up to \~2 years). Both belzutifan and lenvatinib will be administered orally QD until progressive disease or discontinuation.

Group III: Coformulation Vibostolimab/Pembrolizumab+BelzutifanExperimental Treatment2 Interventions

Participants will receive vibostolimab/pembrolizumab (coformulation of 200 mg vibostolimab and pembrolizumab 200 mg). Vibostolimab/pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to \~2 years). Belzutifan will be administered orally QD until progressive disease or discontinuation.

Group IV: Coformulation Pembrolizumab/Quavonlimab + LenvatinibExperimental Treatment2 Interventions

Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 17 administrations (up to \~2 years). Lenvatinib will be administered orally once-daily (QD) until progressive disease or discontinuation.

Group V: Coformulation Favezelimab/Pembrolizumab+ LenvatinibExperimental Treatment2 Interventions

Participants will receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg) PLUS lenvatinib 20 mg. Favezelimab/Pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 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