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)

NCT ID: NCT05468697

Last Updated: 2026-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-10

Study Completion Date

2026-07-21

Brief Summary

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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.

Detailed Description

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Conditions

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Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Belzutifan

Intervention Type DRUG

40 mg tablet administered orally at a dose of 120 mg.

Palbociclib

Intervention Type DRUG

75, 100, or 125 mg tablet administered orally according to randomized dose for 21 days consecutive days followed by 7 days off.

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.

Group Type EXPERIMENTAL

Belzutifan

Intervention Type DRUG

40 mg tablet administered orally at a dose of 120 mg.

Palbociclib

Intervention Type DRUG

75, 100, or 125 mg tablet administered orally according to randomized dose for 21 days consecutive days followed by 7 days off.

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.

Group Type EXPERIMENTAL

Belzutifan

Intervention Type DRUG

40 mg tablet administered orally at a dose of 120 mg.

Palbociclib

Intervention Type DRUG

75, 100, or 125 mg tablet administered orally according to randomized dose for 21 days consecutive days followed by 7 days off.

Interventions

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Belzutifan

40 mg tablet administered orally at a dose of 120 mg.

Intervention Type DRUG

Palbociclib

75, 100, or 125 mg tablet administered orally according to randomized dose for 21 days consecutive days followed by 7 days off.

Intervention Type DRUG

Other Intervention Names

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MK-6482 PT2977 IBRANCE® PD 0332991 WELIREG™

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Georgetown University Medical Center ( Site 1002)

Washington D.C., District of Columbia, United States

Site Status

University of Chicago Medical Center ( Site 1007)

Chicago, Illinois, United States

Site Status

Beth Israel Deaconess Medical Center-Cancer Clinical Trials Office ( Site 1001)

Boston, Massachusetts, United States

Site Status

Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 1004)

Salt Lake City, Utah, United States

Site Status

Macquarie University-MQ Health Clinical Trials Unit ( Site 2001)

Macquarie University, New South Wales, Australia

Site Status

Westmead Hospital ( Site 2006)

Westmead, New South Wales, Australia

Site Status

Frankston Hospital-Oncology and Haematology ( Site 2005)

Frankston, Victoria, Australia

Site Status

One Clinical Research ( Site 2008)

Nedlands, Western Australia, Australia

Site Status

Emek Medical Center-oncology ( Site 3003)

Afula, , Israel

Site Status

Rambam Health Care Campus-Oncology ( Site 3000)

Haifa, , Israel

Site Status

Shaare Zedek Medical Center-Oncology ( Site 3002)

Jerusalem, , Israel

Site Status

Rabin Medical Center-Oncology ( Site 3004)

Petah Tikva, , Israel

Site Status

Sourasky Medical Center ( Site 3005)

Tel Aviv, , Israel

Site Status

Countries

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United States Australia Israel

References

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Meiman D, Skaar TC, Shugg T, Quinney SK. Physiologically Based Pharmacokinetic Model to Assess the Drug-Drug-Gene Interaction Potential of Belzutifan in Combination With Cyclin-Dependent Kinase 4/6 Inhibitors. JCO Precis Oncol. 2025 Jul;9:e2500153. doi: 10.1200/PO-25-00153. Epub 2025 Jul 25.

Reference Type DERIVED
PMID: 40712111 (View on PubMed)

Related Links

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Other Identifiers

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MK-6482-024

Identifier Type: OTHER

Identifier Source: secondary_id

LITESPARK-024

Identifier Type: OTHER

Identifier Source: secondary_id

2023-504963-17-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1290-4845

Identifier Type: REGISTRY

Identifier Source: secondary_id

6482-024

Identifier Type: -

Identifier Source: org_study_id

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