This is an open-label Phase 2 study which will evaluate the efficacy and safety of belzutifan in combination with cabozantinib in participants with advanced ccRCC. Belzutifan and cabozantinib will be administered orally once daily.

Inclusion Criteria:

• Has locally advanced or metastatic RCC with predominantly clear cell subtype

• Has at least one measurable lesion as defined by RECIST version 1.1

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Has adequate organ function defined as follows:

  • Absolute neutrophil count ≥ 1,000/µL, hemoglobin level ≥ 10 g/dL and platelet count ≥ 100,000/µL without transfusion or growth factor support within 2 weeks prior to obtaining the hematology values at screening;
  • Serum creatinine level ≤ 2.0 × upper limit of normal (ULN)
  • Transaminase levels (AST/ALT) ≤ 3.0 × upper limit of normal (ULN); total bilirubin (TBILI) ≤ 1.5 mg/dL in the absence of Gilbert's disease *Cohort 1: Participants must not have received prior systemic therapy for advanced or metastatic ccRCC

• Cohort 2: Participants must have received prior immunotherapy and no more than two prior treatments for advanced or metastatic ccRCC

Exclusion Criteria:

• Has received prior treatment with belzutifan or other HIF2α inhibitors
• Has received prior treatment with cabozantinib
• Has had radiation therapy for bone metastases within two weeks of starting study drug
• Has a history of untreated brain metastases or history of leptomeningeal disease or spinal cord compression
• Has failed to recover from the reversible effects of prior anticancer therapy
• Has uncontrolled or poorly controlled hypertension
• Is receiving anticoagulant therapy
• Has had any major cardiovascular event within 6 months prior to study drug administration
• Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results
• Has had major surgery within 3 months before first study drug administration
• Has an active infection requiring systemic treatment
• Is participating in another therapeutic clinical trial

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf