Recruiting
Phase 3

Belzutifan & Zanzalintinib

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT07489495

Conditions

Carcinoma, Renal Cell

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Belzutifan

Zanzalintinib

Placebo

Study Details

Brief summary:

Researchers are looking for new ways to treat advanced renal cell carcinoma (RCC).

A standard (usual) treatment for certain people with RCC is belzutifan (a study medicine), which is a targeted therapy. Targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread. Researchers want to learn if adding another targeted therapy called zanzalintinib (another study medicine) can treat more people with advanced RCC than belzutifan alone.

The goal of this study is to learn if people who receive belzutifan and zanzalintinib live longer overall and without the cancer getting worse compared to people who receive belzutifan and placebo.

Conditions

Carcinoma, Renal Cell

Study ID

NCT07489495

Start date

Apr 9, 2026

Status verified date

Sep, 2026

Completion date

Nov 27, 2030

Anticipated

Primary completion date

Nov 27, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

  • Has a histologically confirmed diagnosis of unresectable, advanced renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features) ie, Stage IV RCC per American Joint Committee on Cancer (8th Edition)
  • Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
  • Has received no more than 3 prior systemic regimens for RCC, including only 1 prior anti-Programmed Cell Death-1/Programmed Cell Death 1 Ligand 1 therapy

Exclusion Criteria:

For exclusion criteria: The main exclusion criteria include but are not limited to the following:

  • Has any of the following: a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or required chronic supplemental oxygen
  • Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
  • Has deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization
  • Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram
  • Has had major surgery within 8 weeks before randomization
  • Has current pneumonitis/interstitial lung disease
  • Has a history of human immunodeficiency virus infection
  • Has Hepatitis B or Hepatitis C virus infection
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has a history of solid organ transplant
  • Has not adequately recovered from major surgery or has ongoing surgical complications

Study Design

Enrollment

758 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Belzutifan + Zanzalintinib

Participants will receive 120 mg belzutifan orally and 60 mg zanzalintinib once daily for approximately 24 months.

active comparator: Belzutifan + Placebo

Participants will receive 120 mg belzutifan orally and zanzalintinib-matching placebo once daily for approximately 24 months.

Interventions

Belzutifan

Tablet for oral administration.

Zanzalintinib

Tablet for oral administration.

Placebo

Zanzalintinib-matching placebo tablet for oral administration.

Primary outcome measure

  • Progression-free Survival (PFS) [ Time Frame: Up to approximately 30 months ]
  • Overall Survival (OS) [ Time Frame: Up to approximately 50 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839Trialsites@msd.com

Locations

Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0102)

Recruiting

Marietta, Georgia, United States, 30060

Contacts

Study Coordinator

770-281-5124

The West Clinic, P.C. ( Site 0115)

Recruiting

Germantown, Tennessee, United States, 38138

Contacts

Study Coordinator

901-683-0055

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 3, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-03.