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

NCT07405164 | Recruiting Phase 3 FDA Drug

• 5 other identifiers: 6482-043U1111-1325-45822025-524160-38-00MK-6482-043jRCT2061260008
• Study Type: interventional
• Target: 450
• Locations: 6 countries
• Sites: 12

Brief Summary

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.

Conditions

Von Hippel-Lindau Disease; Carcinoma, Renal Cell

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of Participants Who Experience One or More Adverse Events (AE)

  Up to approximately 2 years

• Number of Participants Who Discontinued Study Intervention Due to an AE

  Up to approximately 2 years

Study Arms (3)

Cohort A: Belzutifan Monotherapy

EXPERIMENTAL

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

Cohort B: Belzutifan Combination Therapy

EXPERIMENTAL

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; Drug: Palbociclib; Drug: Nivolumab; Drug: Lenvatinib; Drug: Cabozantinib

Cohort C: Non-Belzutifan Therapy

ACTIVE COMPARATOR

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; Drug: Cabozantinib; Drug: Everolimus

Interventions

Belzutifan DRUG

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.

Also known as: MK-6482, PT2977, WELIREG

Cohort A: Belzutifan Monotherapy; Cohort B: Belzutifan Combination Therapy

Palbociclib DRUG

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.

Cohort B: Belzutifan Combination Therapy

Nivolumab DRUG

Nivolumab is administered intravenously at 480 mg until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.

Cohort B: Belzutifan Combination Therapy

Lenvatinib DRUG

Lenvatinib is administered orally at 20 mg qd until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.

Cohort B: Belzutifan Combination Therapy; Cohort C: Non-Belzutifan Therapy

Cabozantinib DRUG

Cabozantinib is administered orally at 60 mg qd until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.

Cohort B: Belzutifan Combination Therapy; Cohort C: Non-Belzutifan Therapy

Everolimus DRUG

Everolimus is administered orally at 10 mg qd until PD, unacceptable toxicity, withdrawal of consent, death, investigator decision, or study termination.

Cohort C: Non-Belzutifan Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (12)

START San Antonio ( Site 0104)

San Antonio, Texas, 78229, United States

RECRUITING

Rambam Health Care Campus ( Site 1600)

Haifa, 3109601, Israel

RECRUITING

Hadassah Medical Center ( Site 1604)

Jerusalem, 9112001, Israel

RECRUITING

Sourasky Medical Center ( Site 1603)

Tel Aviv, 64239, Israel

RECRUITING

N.N. Blokhin NMRCO ( Site 2101)

Moscow, Moscow, 115478, Russia

RECRUITING

Russian Scientific Center of Radiology and Surgical Technologies ( Site 2100)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

ACTIVE NOT RECRUITING

Samsung Medical Center ( Site 2902)

Gangnam, Seoul, 06351, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System ( Site 2901)

Seodaemun-gu, Seoul, 03722, South Korea

RECRUITING

Asan Medical Center ( Site 2900)

Seoul, 05505, South Korea

RECRUITING

Taipei Veterans General Hospital ( Site 2800)

Taipei, 11217, Taiwan

RECRUITING

ME І.І. Mechnykov Dnipro Regional Clinical Hospital ( Site 2601)

Dnipropetrovsk, Dnipropetrovsk Oblast, 49005, Ukraine

ACTIVE NOT RECRUITING

CNCE Precarpathian Clinical Oncologic Center ( Site 2600)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018, Ukraine

ACTIVE NOT RECRUITING

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

von Hippel-Lindau Disease; Carcinoma, Renal Cell

Interventions

belzutifan; palbociclib; Nivolumab; lenvatinib; cabozantinib; Everolimus

Condition Hierarchy (Ancestors)

Neurocutaneous Syndromes; Nervous System Diseases; Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: February 12, 2026
• Study Start: March 23, 2026
• Primary Completion (Estimated): January 14, 2034
• Study Completion (Estimated): January 14, 2034
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1); KR (3); TW (1); UA (2); RU (2); IL (3)