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)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Renal Cell Carcinoma

Treatments: Drug: Belzutifan; Drug: Palbociclib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05468697

MK-6482-024 (Other Identifier)

6482-024

2023-504963-17-00 (Registry Identifier)

U1111-1290-4845 (Other Identifier)

LITESPARK-024 (Other Identifier)

Details and patient eligibility

About

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. The study will establish the safety of belzutifan plus palbociclib and determine a recommended dosage of palbociclib for the combination therapy by ascending dose escalation.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups

Beltuzifan 120 mg + Palbociclib 75 mg

Experimental group

Description:

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.

Treatment:

Drug: Palbociclib

Drug: Belzutifan

Beltuzifan 120 mg + Palbociclib 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Palbociclib

Drug: Belzutifan

Beltuzifan 120 mg + Palbociclib 125 mg

Experimental group

Description:

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.

Treatment:

Drug: Palbociclib

Drug: Belzutifan