Purpose

Researchers are looking for more ways to treat advanced renal cell carcinoma (RCC) that is recurrent. Researchers want to learn if recurrent advanced renal cell carcinoma (RCC) responds (gets smaller or goes away) after treatment with belzutifan (MK-6482) and zanzalintinib compared to cabozantinib. The goal of this study is to learn if: People who take belzutifan and zanzalintinib live longer overall and without the cancer getting worse than people who take cabozantinib.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

The main inclusion criteria include but are not limited to the following: - Has a histologically confirmed diagnosis of unresectable, advanced renal cell cancer (RCC) with clear cell component (with or without sarcomatoid features) i.e., Stage IV renal cell cancer per American Joint Committee on Cancer (AJCC) (8th Edition) - Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) - Has disease recurrence during adjuvant anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/L1) therapy or recurrence ≤24 months following the last dose of adjuvant anti-PD-1/L1 therapy - Has received no other prior systemic therapy for their RCC except for their adjuvant anti-PD-1/L1 therapy

Exclusion Criteria

The main exclusion criteria include but are not limited to the following: - Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, new-onset angina, pulmonary embolism, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability - Had 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 or has not adequately recovered from major surgery or has ongoing surgical complications - Has current pneumonitis/interstitial lung disease - Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage within 4 weeks prior to randomization - Has a gastrointestinal disorder including those associated with a high risk of perforation or fistula formation - Has a serious active nonhealing wound/ulcer/bone fracture - Has a requirement for hemodialysis or peritoneal dialysis - Has history of human immunodeficiency virus infection - Has hepatitis B or hepatitis C virus - Has pharmacologically uncompensated, symptomatic hypothyroidism - Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Belzutifan plus Zanzalintinib
Participants will receive belzutifan orally once daily (QD) PLUS zanzalintinib orally QD until one of the reasons for discontinuation of study intervention are met.
  • Drug: Belzutifan
    Administered orally QD
    Other names:
    • MK-6482
    • PT2977
    • WELIREG™
  • Drug: Zanzalintinib
    Administered orally QD
    Other names:
    • XL092
Active Comparator
Cabozantinib
Participants will receive cabozantinib orally QD until one of the reasons for discontinuation of study intervention are met.
  • Drug: Cabozantinib
    Administered orally QD

Recruiting Locations

Alaska Oncology and Hematology ( Site 0133)
Anchorage, Alaska 99508
Contact:
Study Coordinator
907-257-9851

New England Cancer Specialists ( Site 0132)
Westbrook, Maine 04092
Contact:
Study Coordinator
207-303-3300

Greater Baltimore Medical Center ( Site 0145)
Baltimore, Maryland 21204
Contact:
Study Coordinator
443-849-8136

Metro-Minnesota Community Clinical Oncology ( Site 0144)
Saint Louis Park, Minnesota 55426
Contact:
Study Coordinator
952-993-1555

Oncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 0131)
Omaha, Nebraska 68130-2042
Contact:
Study Coordinator
402-691-6971

Carolina Oncology Specialists, PA ( Site 9002)
Charlotte, North Carolina 28207
Contact:
Study Coordinator
704-342-1900

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@msd.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.