NCT07489495

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
758

participants targeted

Target at P75+ for phase_3

Timeline
55mo left

Started Apr 2026

Longer than P75 for phase_3

Geographic Reach
4 countries

8 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress3%
Apr 2026Nov 2030

First Submitted

Initial submission to the registry

March 20, 2026

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 24, 2026

Completed
16 days until next milestone

Study Start

First participant enrolled

April 9, 2026

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 27, 2030

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 27, 2030

Last Updated

May 15, 2026

Status Verified

May 1, 2026

Enrollment Period

4.6 years

First QC Date

March 20, 2026

Last Update Submit

May 14, 2026

Conditions

Carcinoma, Renal Cell

Outcome Measures

Primary Outcomes (2)

  • Progression-free Survival (PFS)

    PFS is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first.

    Up to approximately 30 months

  • Overall Survival (OS)

    OS is defined as the time from randomization to death due to any cause.

    Up to approximately 50 months

Secondary Outcomes (12)

  • Objective Response Rate (ORR)

    Up to approximately 30 months

  • Duration of Response (DOR)

    Up to approximately 30 months

  • Number of Participants Who Experience One or More Adverse Events (AEs)

    Up to approximately 25 months

  • Number of Participants who Discontinue Study Treatment Due to an AE

    Up to approximately 24 months

  • Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score

    Baseline and up to approximately 25 months

  • +7 more secondary outcomes

Study Arms (2)

Belzutifan + Zanzalintinib

EXPERIMENTAL

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

Drug: BelzutifanDrug: Zanzalintinib

Belzutifan + Placebo

ACTIVE COMPARATOR

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

Drug: BelzutifanDrug: Placebo

Interventions

BelzutifanDRUG

Tablet for oral administration.

Also known as: MK-6482, PT2977, WELIREG
Belzutifan + PlaceboBelzutifan + Zanzalintinib
ZanzalintinibDRUG

Tablet for oral administration.

Also known as: XL092
Belzutifan + Zanzalintinib
PlaceboDRUG

Zanzalintinib-matching placebo tablet for oral administration.

Belzutifan + Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Centro Privado de RMI Río Cuarto S.A. II ( Site 0255)

Río Cuarto, Córdoba Province, X5800ALB, Argentina

RECRUITING

Centro Oncológico Riojano Integral ( Site 0256)

La Rioja, X5004BAL, Argentina

RECRUITING

Macquarie University ( Site 2700)

Macquarie University, New South Wales, 2109, Australia

SUSPENDED

Rambam Health Care Campus ( Site 1600)

Haifa, 3109601, Israel

RECRUITING

Sheba Medical Center ( Site 1601)

Ramat Gan, 5265601, Israel

RECRUITING

Severance Hospital, Yonsei University Health System ( Site 2903)

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center ( Site 2901)

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center ( Site 2902)

Seoul, 06351, South Korea

RECRUITING

Related Links

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

belzutifan

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Study Officials

  • Medical Director

    Merck Sharp & Dohme LLC

    STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

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

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 20, 2026

First Posted

March 24, 2026

Study Start

April 9, 2026

Primary Completion (Estimated)

November 27, 2030

Study Completion (Estimated)

November 27, 2030

Last Updated

May 15, 2026

Record last verified: 2026-05

Data Sharing

IPD Sharing
Will share

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

More information

Locations

AR(2)KR(3)AU(1)IL(2)