A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033)

Prior treatment

• 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 had major surgery within 8 weeks before randomization or has not adequately recovered from major surgery or has ongoing surgical complications
• Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage within 4 weeks prior to randomization
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

Other illness

• 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
• Has current pneumonitis/interstitial lung disease
• 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 history of human immunodeficiency virus infection
• Has hepatitis B or hepatitis C virus

Lab values

• Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram

Other

• The main exclusion criteria include but are not limited to the following:
• Has a requirement for hemodialysis or peritoneal dialysis
• Has pharmacologically uncompensated, symptomatic hypothyroidism

• 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