A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003)

Peloton Therapeutics

Status and phase: Active, not recruiting; Phase 2

Conditions: Kidney; Renal Cell Cancer Metastatic; Renal Cell Carcinoma Recurrent; Renal Cell Carcinoma (RCC); Renal Cancer; Kidney Cancer; Renal Cell Cancer, Recurrent; Clear Cell Renal Cell Carcinoma (ccRCC); Renal Cell Carcinoma

Treatments: Drug: Cabozantinib; Drug: Belzutifan

Study type: Interventional

Funder types: Industry

Identifiers

NCT03634540

MK-6482-003 (Other Identifier)

6482-003

PT2977-201 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 118 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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118 participants in 2 patient groups

Belzutifan + Cabozantinib: Treatment Naïve (Cohort 1)

Experimental group

Description:

Naïve participants will receive 120 mg belzutifan and 60 mg cabozantinib orally once daily (QD) at the same time.

Treatment:

Drug: Belzutifan

Drug: Cabozantinib

Belzutifan + Cabozantinib: Prior Immunotherapy (Cohort 2)

Experimental group

Description:

Participants who have received prior immunotherapy will receive 120 mg belzutifan and 60 mg cabozantinib orally QD at the same time.

Treatment:

Drug: Belzutifan

Drug: Cabozantinib