A Study of Belzutifan (MK-6482) in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma (MK-6482-024/LITESPARK-024)

Purpose

The purpose of this study is to evaluate the efficacy and safety of belzutifan monotherapy and belzutifan plus palbociclib combination therapy in participants with advanced clear-cell renal cell carcinoma (ccRCC) who experienced disease progression on or after receiving prior therapy. Part 1 will establish the safety of belzutifan plus palbociclib and determine a recommended dosage of palbociclib for the combination therapy by ascending dose escalation. Part 2 will evaluate the efficacy and safety of belzutifan plus palbociclib at the dosage level determined in Part 1.

Condition

  • Renal Cell Carcinoma

Eligibility

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

Inclusion Criteria

  • Has a histologically confirmed diagnosis of unresectable Stage IV (per American Joint Committee on Cancer [AJCC], 8th Edition) RCC with clear-cell component - Has had disease progression on or after having received at least 2 systemic treatments for unresectable Stage IV RCC with prior anti-programmed cell death 1 ligand 1 (PD-1/L1) and a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) in sequence or in combination - Has measurable disease per RECIST 1.1 as assessed by the investigator and verified by blinded independent central review (BICR) - Has recovered from all AEs due to previous therapies

Exclusion Criteria

  • Has hypoxia, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen - Has a known additional malignancy that is progressing or has required active treatment within the past 3 years - Has known central nervous system (CNS) metastases and/or carcinomatous meningitis - Has clinically significant cardiac disease - Has moderate to severe hepatic impairment - Has a known history of human immunodeficiency virus (HIV) infection - Has a history of hepatitis B (HBV) or known active hepatitis C (HCV) infection - Has received prior treatment of belzutifan or palbociclib - Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids - Has had major surgery ≤3 weeks prior to first dose of study intervention - Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin [EPO]) ≤28 days prior to the first dose of study intervention

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1 - Beltuzifan 120 mg + Palbociclib 75 mg 		Participants receive beltuzifan 120 mg orally once per day (QD) and palbociclib 75 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.
  • Drug: Belzutifan
    40 mg tablet administered orally at a dose of 120 mg.
    Other names:
    • WELIREG™
    • MK-6482
    • PT2977
  • Drug: Palbociclib
    75, 100, or 125 mg tablet administered orally according to randomized dose for 21 days consecutive days followed by 7 days off.
    Other names:
    • IBRANCE®
    • PD 0332991
Experimental
Part 1 - Beltuzifan 120 mg + Palbociclib 100 mg 		Participants receive beltuzifan 120 mg orally QD and palbociclib 100 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.
  • Drug: Belzutifan
    40 mg tablet administered orally at a dose of 120 mg.
    Other names:
    • WELIREG™
    • MK-6482
    • PT2977
  • Drug: Palbociclib
    75, 100, or 125 mg tablet administered orally according to randomized dose for 21 days consecutive days followed by 7 days off.
    Other names:
    • IBRANCE®
    • PD 0332991
Experimental
Part 1 - Beltuzifan 120 mg + Palbociclib 125 mg 		Participants receive beltuzifan 120 mg orally QD and palbociclib 125 mg orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation.
  • Drug: Belzutifan
    40 mg tablet administered orally at a dose of 120 mg.
    Other names:
    • WELIREG™
    • MK-6482
    • PT2977
  • Drug: Palbociclib
    75, 100, or 125 mg tablet administered orally according to randomized dose for 21 days consecutive days followed by 7 days off.
    Other names:
    • IBRANCE®
    • PD 0332991
Experimental
Part 2 - Beltuzifan 120 mg + Palbociclib 		Participants receive beltuzifan 120 mg orally QD and palbociclib orally QD in a 28-day schedule (21 days on followed by 7 days off), until progressive disease or discontinuation. Palbociclib will be administered at a dosage level determined in Part 1.
  • Drug: Belzutifan
    40 mg tablet administered orally at a dose of 120 mg.
    Other names:
    • WELIREG™
    • MK-6482
    • PT2977
  • Drug: Palbociclib
    75, 100, or 125 mg tablet administered orally according to randomized dose for 21 days consecutive days followed by 7 days off.
    Other names:
    • IBRANCE®
    • PD 0332991
Experimental
Part 2 - Beltuzifan 120 mg 		Participants receive beltuzifan 120 mg orally QD until progressive disease or discontinuation.
  • Drug: Belzutifan
    40 mg tablet administered orally at a dose of 120 mg.
    Other names:
    • WELIREG™
    • MK-6482
    • PT2977

Recruiting Locations

Georgetown University Medical Center ( Site 1002)
Washington, District of Columbia 20007
Contact:
Study Coordinator
617-797-5460

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

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