Immune + Targeted Therapies for Renal Cell Carcinoma

Recruiting in Palo Alto (17 mi)

+51 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Merck Sharp & Dohme Corp.

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Substudy 03B 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 03B is to evaluate the safety and efficacy of experimental combinations of investigational agents in participants with advanced second line plus (2L+) 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.

Eligibility Criteria

This trial is for adults with advanced renal cell carcinoma who've seen their cancer progress after treatment with specific systemic therapies. They must be able to take oral meds, have good organ function, controlled blood pressure, and no recent major surgery or active infections. Women of childbearing potential must use contraception and not be pregnant or breastfeeding.

Inclusion Criteria

I am not pregnant, breastfeeding, and if able to bear children, I am using contraception or abstaining from sex.

My kidney cancer worsened after treatment with specific immune or targeted therapies.

I can take pills by mouth.

See 6 more

Exclusion Criteria

I have an autoimmune disease but haven't needed systemic treatment in the last 2 years.

I have been treated with belzutifan before.

I have a preexisting abnormal connection between two parts inside my body.

See 17 more

Treatment Details

Interventions

Favezelimab (Other)
MK-4830 (Other)
Pembrolizumab (Monoclonal Antibodies)
Quavonlimab (Other)

Trial OverviewThe study tests combinations of experimental drugs (MK-4830, Pembrolizumab/Quavonlimab, Favezelimab/Pembrolizumab) in two phases: first ensuring safety (no severe reactions), then checking if they work against kidney cancer that's worsened despite previous treatments.

Participant Groups

6Treatment groups

Experimental Treatment

Group I: Pembrolizumab + MK-4830Experimental Treatment2 Interventions

Participants will receive pembrolizumab 200 mg PLUS MK-4830 800 mg. Both pembrolizumab and MK-4830 will be administered IV Q3W for up to 35 administrations (up to \~2 years).

Group II: 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 III: Pembrolizumab + BelzutifanExperimental Treatment2 Interventions

Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to \~ 2 years). Belzutifan will be administered orally once-daily (QD) until progressive disease or discontinuation.

Group IV: Coformulation Pembrolizumab/QuavonlimabExperimental Treatment1 Intervention

Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg). Pembrolizumab/quavonlimab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 17 administrations (up to \~2 years).

Group V: Coformulation Favezelimab/PembrolizumabExperimental Treatment1 Intervention

Participants will receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg). Favezelimab/Pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to \~2 years).

Group VI: Belzutifan + LenvatinibExperimental Treatment2 Interventions

Participants will receive Belzutifan 120 mg PLUS lenvatinib 20 mg. Both belzutifan and lenvatinib will be administered orally QD until progressive disease or discontinuation.