Purpose

This study will compare the efficacy and safety of belzutifan + lenvatinib versus cabozantinib in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy. The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival.

Condition

Eligibility

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

Inclusion Criteria

  • Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC). - Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment or neoadjuvant/adjuvant with progression on or within 6 months of last dose. - Measurable disease per RECIST 1.1 criteria as assessed by local study investigator. - Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization. - Received no more than 2 prior systemic regimens including: one anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with progression on or within 6 months from the last dose of that regimen OR one or 2 regimens for locoregional/advanced disease - Received only 1 prior antiPD-1/L1 therapy for adjuvant, neoadjuvant/adjuvant or locally advanced/metastatic RCC. - A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib. - A female participant is eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention in the belzutifan+ lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm. - Adequately controlled blood pressure. - Adequate organ function.

Exclusion Criteria

  • A pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen. - Known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy. - Known central nervous system (CNS) metastases and/or carcinomatous meningitis. - Clinically significant cardiac disease within 6 months of first dose of study intervention. - Prolongation of QTc interval to >480 ms. - Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable. - Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula. - Moderate to severe hepatic impairment. - History of significant bleeding within 3 months before randomization. - History of solid organ transplantation. - Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study. - Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption). - Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations. - Received colony-stimulating factors [eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)] within 28 days before randomization. - Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor. - Prior treatment with lenvatinib. - Prior treatment with cabozantinib. - Currently participating in a study of an investigational agent or using an investigational device. - Active infection requiring systemic therapy. - History of human immunodeficiency virus (HIV) infection. - History of hepatitis B or known active hepatitis C infection.

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 + Lenvatinib
Belzutifan 120 mg and lenvatinib 20 mg orally once a day
  • Drug: Belzutifan
    Immediate-release 40 mg tablet
    Other names:
    • PT2977
    • MK-6482
    • WELIREG™
  • Drug: Lenvatinib
    Capsule available in 4 mg and 10 mg dosages
    Other names:
    • Lenvima
    • E7080
    • MK-7902
Active Comparator
Cabozantinib
Cabozantinib 60 mg orally once a day
  • Drug: Cabozantinib
    Tablet available in 20 mg, 40 mg and 60 mg dosages
    Other names:
    • Cabometyx
    • Cometriq
    • XL184
    • BMS-907351

More Details

Status
Active, not recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

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.