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: 22 countries
• Sites: 49

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; Malignant Neoplasms

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: 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

Interventions

Belzutifan DRUG

Belzutifan is administered orally at 120 mg once daily (qd) OR 200 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

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

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 (49)

Beth Israel Deaconess Medical Center ( Site 0107)

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute ( Site 0105)

Boston, Massachusetts, 02215, United States

RECRUITING

Karmanos Cancer Center ( Site 0108)

Detroit, Michigan, 48201, United States

RECRUITING

Hospital of the University of Pennsylvania Perelman Center for Advanced Medicine ( Site 0100)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

SCRI Oncology Partners ( Site 7000)

Nashville, Tennessee, 37203, United States

RECRUITING

START San Antonio ( Site 0104)

San Antonio, Texas, 78229, United States

RECRUITING

Fred Hutchinson Cancer Center ( Site 0106)

Seattle, Washington, 98109, United States

RECRUITING

St George Hospital-Oncology Clinical Research Unit ( Site 2701)

Kogarah, New South Wales, 2217, Australia

RECRUITING

Westmead Hospital ( Site 2703)

Sydney, New South Wales, 2145, Australia

RECRUITING

UZ Leuven ( Site 0900)

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

BP - A Beneficencia Portuguesa de São Paulo ( Site 0200)

São Paulo, São Paulo, 01323-001, Brazil

RECRUITING

Département clinique de médecine de laboratoire du CHUM ( Site 0001)

Montreal, Quebec, H3T 1E2, Canada

ACTIVE NOT RECRUITING

James Lind Centro de Investigacion del Cancer ( Site 0304)

Temuco, Araucania, 4800827, Chile

RECRUITING

CIDO SpA ( Site 0305)

Temuco, Araucania, 4810148, Chile

RECRUITING

FALP ( Site 0300)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Oncovida ( Site 0303)

Santiago, Region M. de Santiago, 7500994, Chile

RECRUITING

Bradfordhill ( Site 0301)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

ONCOCENTRO APYS ( Site 0302)

Viña del Mar, Valparaiso, 2520598, Chile

RECRUITING

Fakultni nemocnice Olomouc-Onkologicka klinika ( Site 1000)

Olomouc, 77900, Czechia

RECRUITING

Herlev and Gentofte Hospital ( Site 1200)

Herlev, Capital Region, 2370, Denmark

RECRUITING

Tampereen yliopistollinen sairaala ( Site 1305)

Tampere, Pirkanmaa, 33520, Finland

RECRUITING

Hôpitaux Universitaires de Strasbourg ( Site 1702)

Strasbourg, Bas-Rhin, 67200, France

RECRUITING

Institut Claudius Regaud ( Site 1703)

Toulouse, Haute-Garonne, 31059, France

RECRUITING

Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 1501)

Budapest, 1122, Hungary

RECRUITING

Rambam Health Care Campus ( Site 1600)

Haifa, 3109601, Israel

RECRUITING

Hadassah Medical Center ( Site 1604)

Jerusalem, 9112001, Israel

RECRUITING

Rabin Medical Center ( Site 1602)

Petah Tikva, 4941492, Israel

RECRUITING

Sheba Medical center ( Site 1601)

Ramat Gan, 5265601, Israel

RECRUITING

Sourasky Medical Center ( Site 1603)

Tel Aviv, 64239, Israel

RECRUITING

Kyushu University Hospital ( Site 3101)

Fukuoka, 812-8582, Japan

RECRUITING

Maastricht Universitair Medisch Centrum - MUMC ( Site 1900)

Maastricht, Limburg, 6229 HX, Netherlands

RECRUITING

Isala, locatie Zwolle ( Site 1902)

Zwolle, Overijssel, 8025 AB, Netherlands

RECRUITING

Auckland City Hospital ( Site 3000)

Auckland, 1023, New Zealand

RECRUITING

Zakład Diagnostyki Laboratoryjnej, Centrum Onkologii ( Site 2000)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796, Poland

RECRUITING

N.N. Blokhin NMRCO ( Site 2101)

Moscow, Moscow, 115478, Russia

ACTIVE NOT 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

Hospital Universitari Vall d'Hebron ( Site 2300)

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario 12 de Octubre ( Site 2301)

Madrid, 28041, Spain

RECRUITING

Taipei Veterans General Hospital ( Site 2800)

Taipei, 11217, Taiwan

ACTIVE NOT RECRUITING

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

Dnipropetrovsk, Dnipropetrovsk Oblast, 49005, Ukraine

RECRUITING

CNCE Precarpathian Clinical Oncologic Center ( Site 2600)

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

ACTIVE NOT RECRUITING

The Beatson West of Scotland Cancer Centre ( Site 2505)

Glasgow, Glasgow City, G12 0YN, United Kingdom

RECRUITING

St Bartholomew's Hospital ( Site 2500)

London, London, City of, EC1A 7BE, United Kingdom

RECRUITING

ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 2502)

London, London, City of, SW3 6JJ, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust, Charing Cross Hospital ( Site 2504)

London, London, City of, W6 8RF, United Kingdom

RECRUITING

The Christie NHS Foundation Trust ( Site 2501)

Manchester, M20 4BX, United Kingdom

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

von Hippel-Lindau Disease; Neoplasms

Interventions

belzutifan; Nivolumab; lenvatinib; cabozantinib

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: July 27, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

BR (1); CA (1); BE (1); FR (2); AU (2); DK (1); PL (1); NZ (1); CL (6); US (7); KR (3); TW (1); UA (2); RU (2); IL (5); ES (2); NL (2); HU (1); CZ (1); GB (5); FI (1); JP (1)