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Renal Cell CarcinomaPhase 1/2NCT05468697

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)

A Phase 1/2 study testing Belzutifan and Palbociclib in people with Renal Cell Carcinoma, run by Merck Sharp & Dohme LLC at 13 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Carcinoma
What is being tested?
Belzutifan and Palbociclib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
13 sitesin 3 countries
Study dates
10 Aug 2022to 22 Dec 2026
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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 locations and contacts

13 sites in 3 countries.

13 sites in 3 countries

Israel5 sites

  • Emek Medical Center-oncology ( Site 3003)

    Afula, 1834111

  • Rambam Health Care Campus-Oncology ( Site 3000)

    Haifa, 3109601

  • Shaare Zedek Medical Center-Oncology ( Site 3002)

    Jerusalem, 9103102

  • Rabin Medical Center-Oncology ( Site 3004)

    Petah Tikva, 4941492

  • Sourasky Medical Center ( Site 3005)

    Tel Aviv, 6423906

Other trials in Israel

United States4 sites

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

    Boston, Massachusetts, 02215

  • University of Chicago Medical Center ( Site 1007)

    Chicago, Illinois, 60637

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

    Salt Lake City, Utah, 84112

  • Georgetown University Medical Center ( Site 1002)

    Washington D.C., District of Columbia, 20007

Other trials in United States

Australia4 sites

  • Frankston Hospital-Oncology and Haematology ( Site 2005)

    Frankston, Victoria, 3199

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

    Macquarie University, New South Wales, 2109

  • One Clinical Research ( Site 2008)

    Nedlands, Western Australia, 6009

  • Westmead Hospital ( Site 2006)

    Westmead, New South Wales, 2145

Other trials in Australia

About this study

Official title: A Multicenter, Open-label, Randomized, Phase 1/2 Study of Belzutifan in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma

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.

Being tested
Belzutifan, Palbociclib
Keywords
Programmed cell death ligand 1 (PD-L1), Hypoxia inducible factor 2 alpha (HIF-2 alpha), Hypoxia inducible factor 2α (HIF-2α), Renal Cell Carcinoma (RCC), Kidney Cancer
Medical subject headings
Carcinoma, Renal Cell, Kidney Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BelzutifanDrug

    Also called WELIREG™, MK-6482, PT2977

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

  • PalbociclibDrug

    Also called IBRANCE®, PD 0332991

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

Study groups in NCT05468697
Study groupRoleWhat they receive
Beltuzifan 120 mg + Palbociclib 75 mgExperimentalParticipants 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.
Receives: Drug: Belzutifan; Drug: Palbociclib
Beltuzifan 120 mg + Palbociclib 100 mgExperimentalParticipants 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.
Receives: Drug: Belzutifan; Drug: Palbociclib
Beltuzifan 120 mg + Palbociclib 125 mgExperimentalParticipants 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.
Receives: Drug: Belzutifan; Drug: Palbociclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)

    A DLT consists of one or more of the following toxicities: Grade (Gr) 3 or 4 hypoxia or dyspnea; Gr 3 or 4 nausea, vomiting, or diarrhea if persistent for >48 hours despite therapy; Gr 3 or 4 cardiovascular, vascular, or thrombotic events; Nonhematologic AE ≥Gr 3 in severity with exceptions; Gr 3 rash that does not resolve within 2 weeks; Gr 3 nonhematologic toxicity if persisting despite optimal medical treatment; Gr 3 or 4 hematologic toxicities; Gr 3 or 4 febrile neutropenia; Gr 3 or 4 nonhematologic laboratory value; Any aspartate aminotransferase or alanine aminotransferase >8x the upper limit of normal (ULN) or 5 to 8x ULN persisting for >2 weeks; >2 weeks delay in dosing due to intervention-related toxicity; Intervention-related toxicity causing intervention discontinuation in the first 28 days of dosing; Missing >20% of intervention doses due to drug-related AEs; Gr 5 toxicity. The number of participants who experience at least one DLT will be reported.

    Measured: Up to approximately 28 days

  2. Number of Participants Who Experience at Least One Adverse Event (AE)

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience at least one AE will be reported.

    Measured: Up to approximately 4 years

  3. Number of Participants Who Discontinue Study Treatment Due to an AE

    An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. The number of participants who discontinued from the study treatment due to an AE will be reported.

    Measured: Up to approximately 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2022
  2. Study start10 Aug 2022
  3. Primary completion22 Dec 2026 (estimated)
  4. Study completion22 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05468697
Sponsor's protocol ID
6482-024
Other IDs
MK-6482-024, LITESPARK-024, 2023-504963-17-00, U1111-1290-4845, 2023
Status last verified
Oct 2026
First submitted
18 Jul 2022
Last updated
27 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 40712111

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Belzutifan and Palbociclib in people with Renal Cell Carcinoma, run by Merck Sharp & Dohme LLC at 13 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Israel, United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT) (time frame: Up to approximately 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05468697, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.

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