Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043)

A Multicenter, Open-label, Phase 3 Extension Study to Evaluate the Long-term Efficacy and Safety in Participants Who Are Currently on Treatment in a Belzutifan Study (LITESPARK-043)

Researchers are looking for new ways to treat advanced solid tumors and von Hippel-Lindau (VHL)-related tumors:

• Advanced means the cancer has spread to other parts of the body (metastatic) or cannot be removed with surgery
• Solid tumors are cancers mostly in body organs and tissues, not in the blood or other body liquids
• VHL-related tumors are tumors caused by VHL disease. VHL disease is passed down from parents to children and people with VHL disease have a higher chance of getting certain types of cancer

Researchers want to learn about the long-term effects of a trial medicine called belzutifan. Belzutifan, also called MK-6482, is designed to block a protein that helps tumors grow and survive. This is an extension trial, which means only people who were in certain other belzutifan trials (called parent trials) may be able to join. The goal of this trial is to learn how long people live after they start taking belzutifan.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Renal Cell; Von Hippel-Lindau Disease
• Intervention / Treatment: Drug: Belzutifan; Drug: Palbociclib; Drug: Nivolumab; Drug: Lenvatinib; Drug: Cabozantinib; Drug: Everolimus

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@msd.com

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • UZ Leuven ( Site 0900)
      • Contact: Study Coordinator; Phone Number: +32 (0)16 34 69 12
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus ( Site 1600)
    • Contact: Study Coordinator; Phone Number: +97247772688
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center ( Site 1604)
    • Contact: Study Coordinator; Phone Number: +97226777333
  • Tel Aviv, Israel, 64239
    • Recruiting
    • Sourasky Medical Center ( Site 1603)
    • Contact: Study Coordinator; Phone Number: + 972 3 6947284
• Russia
  • Moscow
    • Moscow, Moscow, Russia, 115478
      • Recruiting
      • N.N. Blokhin NMRCO ( Site 2101)
      • Contact: Study Coordinator; Phone Number: +79037380779
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 197758
      • Active, not recruiting
      • Russian Scientific Center of Radiology and Surgical Technologies ( Site 2100)
• South Korea
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center ( Site 2900)
    • Contact: Study Coordinator; Phone Number: +82-2-3010-5977
  • Seoul
    • Gangnam, Seoul, South Korea, 06351
      • Recruiting
      • Samsung Medical Center ( Site 2902)
      • Contact: Study Coordinator; Phone Number: +82-2-3410-1767
    • Seodaemun-gu, Seoul, South Korea, 03722
      • Recruiting
      • Severance Hospital, Yonsei University Health System ( Site 2901)
      • Contact: Study Coordinator; Phone Number: +82-2-2228-8138
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre ( Site 2301)
    • Contact: Study Coordinator; Phone Number: +34 91 390 83 39
• Taiwan
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital ( Site 2800)
    • Contact: Study Coordinator; Phone Number: +886228712121x86341
• Ukraine
  • Dnipropetrovsk Oblast
    • Dnipropetrovsk, Dnipropetrovsk Oblast, Ukraine, 49005
      • Active, not recruiting
      • ME І.І. Mechnykov Dnipro Regional Clinical Hospital ( Site 2601)
  • Ivano-Frankivsk Oblast
    • Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine, 76018
      • Active, not recruiting
      • CNCE Precarpathian Clinical Oncologic Center ( Site 2600)
• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Center ( Site 0108)
      • Contact: Study Coordinator; Phone Number: 800-527-6266
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • START San Antonio ( Site 0104)
      • Contact: Study Coordinator; Phone Number: 210-593-5265

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Participants with advanced solid tumors or von Hippel-Lindau-related neoplasms who are participating in belzutifan-containing studies and on active treatment in a belzutifan parent study.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• Has an on-going serious adverse event in the parent study, unless no longer hospitalized and considered clinically stable.
• Is currently on a dose interruption due to an Adverse Event (AE) in the parent study; once treatment has been resumed in the parent study, the participant is eligible to enroll.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Belzutifan Monotherapy; Participants on active treatment assigned to belzutifan monotherapy in a parent study are transitioned to this extension study. Participants will continue the same dose and frequency of intervention as they were receiving in the parent study at the time of the transition. Treatment will continue until progressive disease (PD), unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.	Drug: Belzutifan; Belzutifan is administered orally at 120 mg once daily (qd) OR 160 mg twice daily (bid) OR 160 mg three times daily (tid) OR 200 mg qd OR 240 mg qd until progressive disease (PD), unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.; Other Names: MK-6482, PT2977, WELIREG
Experimental: Cohort B: Belzutifan Combination Therapy; Participants on active treatment assigned to a belzutifan combination therapy in a parent study are transitioned to this extension study. Participants will continue the same dose and frequency of intervention as they were receiving in the parent study at the time of the transition. Treatment will continue until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.	Drug: Belzutifan; Belzutifan is administered orally at 120 mg once daily (qd) OR 160 mg twice daily (bid) OR 160 mg three times daily (tid) OR 200 mg qd OR 240 mg qd until progressive disease (PD), unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.; Other Names: MK-6482, PT2977, WELIREG; Drug: Palbociclib; Palbociclib is administered orally at 75 mg qd OR 100 mg qd OR 125 mg qd for 21 consecutive days; 7 days off, until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.; Drug: Nivolumab; Nivolumab is administered intravenously at 480 mg until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.; Drug: Lenvatinib; Lenvatinib is administered orally at 20 mg qd until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.; Drug: Cabozantinib; Cabozantinib is administered orally at 60 mg qd until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.
Active Comparator: Cohort C: Non-Belzutifan Therapy; Participants on active treatment assigned to a non-belzutifan therapy in a parent study are transitioned to this extension study. Participants will continue the same dose and frequency of intervention as they were receiving in the parent study at the time of the transition. Treatment will continue until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.	Drug: Lenvatinib; Lenvatinib is administered orally at 20 mg qd until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.; Drug: Cabozantinib; Cabozantinib is administered orally at 60 mg qd until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.; Drug: Everolimus; Everolimus is administered orally at 10 mg qd until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort A and Cohort B: Overall Survival (OS)	Overall survival is defined as the time from randomization or the first dose of any study intervention in the parent study to death due to any cause.	Up to approximately 7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience One or More Adverse Events (AE)	An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.	Up to approximately 2 years
Number of Participants Who Discontinued Study Intervention Due to an AE	An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2026
• Primary Completion (Estimated): January 14, 2034
• Study Completion (Estimated): January 14, 2034

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: February 5, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ciliopathies; Urogenital Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Congenital Abnormalities; Abnormalities, Multiple; Kidney Neoplasms; Neurocutaneous Syndromes; Angiomatosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Carcinoma, Renal Cell; von Hippel-Lindau Disease; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Sirolimus; Nivolumab; Everolimus; cabozantinib; palbociclib; belzutifan; lenvatinib
• Other Study ID Numbers: 6482-043; U1111-1325-4582 (Registry Identifier: UTN); 2025-524160-38-00 (Registry Identifier: EU CT); MK-6482-043 (Other Identifier: MSD); jRCT2061260008 (Registry Identifier: Japan Registry of Clinical Trial (jRCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No