Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)

NCT04924075 | Recruiting Phase 2 FDA Drug

• 6 other identifiers: 6482-015MK-6482-015PT2977jRCT20112200242023-504853-11-002020-005028-13
• Study Type: interventional
• Target: 322
• Locations: 22 countries
• Sites: 84

Brief Summary

This is a study to evaluate the efficacy and safety of belzutifan monotherapy in participants with advanced pheochromocytoma/paraganglioma (PPGL), pancreatic neuroendocrine tumor (pNET), von Hippel-Lindau (VHL) disease-associated tumors, advanced wt (wild-type) gastrointestinal stromal tumor (wt GIST), or advanced solid tumors with hypoxia inducible factor-2 alpha (HIF-2α) related genetic alterations. The primary objective of the study is to evaluate the objective response rate (ORR) of belzutifan per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

Conditions

HIF-2α Mutated Cancers; Pheochromocytoma/Paraganglioma; Pancreatic Neuroendocrine Tumor; Von Hippel-Lindau Disease; Advanced Gastrointestinal Stromal Tumor

Keywords

HIF-2α; Pheochromocytoma/paraganglioma; Pancreatic NET

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)

  ORR is the percentage of participants with complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of the diameters of target lesions) until progressive disease (PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progression) or death due to any cause, whichever occurs first.

  Up to approximately 5.5 years

Secondary Outcomes (8)

• Duration of Response (DOR) as Assessed by BICR

  Up to approximately 5.5 years

• Time to Response (TTR) as Assessed by BICR

  Up to approximately 5.5 years

• Disease Control Rate (DCR) as Assessed by BICR

  Up to approximately 5.5 years

• Progressive Free Survival (PFS) as Assessed by BICR

  Up to approximately 5.5 years

• Overall Survival (OS)

  Up to approximately 5.5 years

Study Arms (1)

Belzutifan

EXPERIMENTAL

Belzutifan, 120 mg, oral, once daily (QD) until progressive disease or discontinuation.

Drug: Belzutifan

Interventions

Belzutifan DRUG

Belzutifan, 120 mg, oral, once daily (QD) until progressive disease or discontinuation.

Also known as: MK-6482, WELIREG™

Belzutifan

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants at least 12 years of age (at least 18 years of age for Cohort B1)
• Diagnosis of one of the following: Advanced/metastatic pheochromocytoma/paraganglioma (PPGL), pancreatic neuroendocrine tumors (pNET), von Hippel-Lindau (VHL) disease associated localized tumors, or advanced wild-type gastrointestinal stromal tumor (wt GIST) or advanced solid tumors with Hypoxia Inducible Factor- 2 alpha subunit (HIF-2α) related genetic alterations
• Cohort BI: VHL Disease-associated tumors:
• Have a diagnosis of VHL disease as determined by a germline test locally and/or clinical diagnosis
• Must be ≥18 years of age
• Has a life expectancy of at least 3 months

You may not qualify if:

• Unable to swallow orally administered medication or has a disorder that might affect the absorption of belzutifan
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• Any of the following: A pulse oximeter reading \<92% at rest, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
• Clinically significant cardiac disease, including unstable angina, acute myocardial infarction, or arterial bypass (CABG) or Percutaneous transluminal coronary angioplasty (PTCA) ≤6 months from study entry, or New York Heart Association Class III or IV congestive heart failure
• Received prior treatment (except somatostatin analogs) with chemotherapy, targeted therapy, biologics, or other investigational therapy within the past 4 weeks of first dose of study intervention

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (84)

Cedars-Sinai Medical Center ( Site 0110)

Los Angeles, California, 90048, United States

RECRUITING

Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0130)

Chicago, Illinois, 60611, United States

RECRUITING

Northwestern Medicine Cancer Center - Warrenville ( Site 0134)

Warrenville, Illinois, 60555, United States

RECRUITING

University of Iowa ( Site 0104)

Iowa City, Iowa, 52242, United States

RECRUITING

Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - Developmental Therapeutics ( Site 0108)

Baltimore, Maryland, 21287, United States

RECRUITING

National Institutes of Health ( Site 0125)

Bethesda, Maryland, 20892, United States

RECRUITING

Massachusetts General Hospital ( Site 0111)

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan ( Site 0126)

Ann Arbor, Michigan, 48109, United States

RECRUITING

Washington University-Internal Medicine/Oncology ( Site 0124)

St Louis, Missouri, 63110, United States

COMPLETED

Icahn School of Medicine at Mount Sinai ( Site 0123)

New York, New York, 10029, United States

COMPLETED

Penn Medicine: University of Pennsylvania Health System-Heme/Onc ( Site 0127)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

SCRI Oncology Partners ( Site 7000)

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt University Medical Center ( Site 0107)

Nashville, Tennessee, 37232, United States

RECRUITING

University of Texas MD Anderson Cancer Center ( Site 0112)

Houston, Texas, 77030, United States

RECRUITING

Prince of Wales Hospital-Medical Oncology ( Site 1601)

Randwick, New South Wales, 2031, Australia

RECRUITING

The Royal Melbourne Hospital ( Site 1602)

Parkville, Victoria, 3050, Australia

RECRUITING

Arthur J.E. Child Comprehensive Cancer Centre ( Site 0203)

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

Princess Margaret Cancer Centre ( Site 0202)

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

FALP ( Site 2200)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Centro de Oncología de Precisión ( Site 2203)

Santiago, Region M. de Santiago, 7560908, Chile

RECRUITING

Peking University First Hospital-Urology ( Site 1900)

Beijing, Beijing Municipality, 100034, China

COMPLETED

Sun Yat-sen University Cancer Center ( Site 1905)

Guangzhou, Guangdong, 510700, China

RECRUITING

Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1904)

Shanghai, Shanghai Municipality, 200001, China

ACTIVE NOT RECRUITING

West China Hospital of Sichuan University ( Site 1906)

Chengdu, Sichuan, 610041, China

COMPLETED

Rigshospitalet ( Site 0304)

Copenhagen, Capital Region, 2100, Denmark

RECRUITING

Rigshospitalet-Department of Endocrinology ( Site 0303)

Copenhagen, Capital Region, 2100, Denmark

RECRUITING

Odense Universitetshospital ( Site 0302)

Odense, Region Syddanmark, 5000, Denmark

RECRUITING

CHU Strasbourg-Hautepierre-Medecine Interne, Endocrinologie et Nutrition ( Site 0402)

Strasbourg, Alsace, 67098, France

RECRUITING

Hôpital Edouard Herriot-oncologie ( Site 0405)

Lyon, Auvergne-Rhône-Alpes, 69003, France

RECRUITING

Institut Paoli-Calmettes-Oncology ( Site 0406)

Marseille, Bouches-du-Rhone, 13009, France

COMPLETED

Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre ( Site 0407)

Le Kremlin-Bicêtre, Paris, 94270, France

RECRUITING

Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0404)

Paris, 75014, France

RECRUITING

Gustave Roussy ( Site 0403)

Villejuif, Île-de-France Region, 94805, France

RECRUITING

Universitaetsklinikum Freiburg ( Site 0504)

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

RECRUITING

Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Department of Internal Medicine IV, Division ( Site 0501)

München, Bavaria, 80336, Germany

COMPLETED

Comprehensive Cancer Center Mainfranken-Div. of Endocrinology and Diabetes ( Site 0500)

Würzburg, Bavaria, 97080, Germany

RECRUITING

Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 0505)

Düsseldorf, North Rhine-Westphalia, 40225, Germany

RECRUITING

Charité Universitaetsmedizin Berlin - Campus Mitte-Department of Endocrinology and Metabolism ( Site 0503)

Berlin, 10117, Germany

RECRUITING

Semmelweis University-Belgyógyászati és Onkológiai Klinika Hematológia Osztály ( Site 0600)

Budapest, 1083, Hungary

RECRUITING

Sheba Medical Center-Institute of Endocrinology, Diabetes and Metabolism ( Site 1400)

Ramat Gan, 5262100, Israel

RECRUITING

Sourasky Medical Center ( Site 1401)

Tel Aviv, 6423906, Israel

RECRUITING

University of Naples Federico II-Dipartimento di Medicina Clinica e Chirurgia ( Site 0704)

Naples, Campania, 80100, Italy

COMPLETED

Fondazione IRCCS Istituto Nazionale dei Tumori-S.C. Oncologia Medica 2- Sarcomi ( Site 0709)

Milan, Lombardy, 20133, Italy

RECRUITING

Azienda Ospedaliero Universitaria Senese-U.O.C. Immunoterapia Oncologica ( Site 0706)

Siena, Tuscany, 53100, Italy

RECRUITING

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola ( Site 0708)

Bologna, 40138, Italy

RECRUITING

Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0701)

Brescia, 25123, Italy

RECRUITING

Ospedale San Raffaele-Oncologia Medica ( Site 0705)

Milan, 20132, Italy

COMPLETED

Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroe ( Site 0700)

Milan, 20141, Italy

RECRUITING

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma ( Site 0703)

Verona, 37134, Italy

RECRUITING

Hokkaido University Hospital ( Site 1800)

Sapporo, Hokkaido, 060-8648, Japan

ACTIVE NOT RECRUITING

Yokohama City University Hospital ( Site 1804)

Yokohama, Kanagawa, 236-0004, Japan

COMPLETED

Kochi Medical School Hospital ( Site 1807)

Nankoku, Kochi, 783-8505, Japan

ACTIVE NOT RECRUITING

National Cancer Center Hospital ( Site 1802)

Chuo-ku, Tokyo, 104-0045, Japan

ACTIVE NOT RECRUITING

Kyoto University Hospital ( Site 1806)

Kyoto, 606-8507, Japan

ACTIVE NOT RECRUITING

Tokyo Women's Medical University Adachi Medical Center ( Site 1803)

Tokyo, 123-8558, Japan

ACTIVE NOT RECRUITING

Universitair Medisch Centrum Utrecht ( Site 1530)

Utrecht, 3584 CX, Netherlands

RECRUITING

Oslo Universitetssykehus Radiumhospitalet ( Site 2400)

Oslo, 0424, Norway

RECRUITING

START Lisbon - Hospital de Santa Maria ( Site 2601)

Lisbon, Lisbon District, 1649-035, Portugal

RECRUITING

Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 2600)

Porto, 4200-072, Portugal

RECRUITING

GBUZ Republican Clinical Oncological Dispensary ( Site 0804)

Ufa, Baskortostan, Respublika, 450054, Russia

COMPLETED

Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov ( Site 0805)

Saint Petersburg, Leningradskaya Oblast', 190020, Russia

COMPLETED

Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 0803)

Saint Petersburg, Leningradskaya Oblast', 198255, Russia

RECRUITING

Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 0801)

Moscow, Moscow, 115522, Russia

RECRUITING

Endocrinology Research Center of Rosmedtechnologies-Surgery ( Site 0809)

Moscow, Moscow, 117036, Russia

COMPLETED

National Cancer Centre Singapore ( Site 1700)

Singapore, Central Singapore, 168583, Singapore

RECRUITING

Seoul National University Hospital ( Site 2001)

Jongno-gu, Seoul, 03080, South Korea

RECRUITING

Asan Medical Center ( Site 2000)

Songpa-gu, Seoul, 05505, South Korea

RECRUITING

MD Anderson Cancer Center-Oncology ( Site 1102)

Madrid, Madrid, Comunidad de, 28033, Spain

COMPLETED

Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1103)

Madrid, Madrid, Comunidad de, 28041, Spain

RECRUITING

Hospital Universitario Central de Asturias-Medical Oncology ( Site 1101)

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Hospital Universitari Vall d'Hebron ( Site 1100)

Barcelona, 08035, Spain

RECRUITING

Skanes University Hospital Lund ( Site 1200)

Lund, Skåne County, 221 85, Sweden

RECRUITING

Karolinska Universitetssjukhuset Solna ( Site 1202)

Stockholm, Stockholm County, 171 76, Sweden

COMPLETED

Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1201)

Uppsala, Uppsala County, 751 85, Sweden

RECRUITING

Sahlgrenska Universitetssjukhuset-Department of Oncology CTU Clinical Trial Unit ( Site 1204)

Gothenburg, Västra Götaland County, 413 45, Sweden

RECRUITING

Baskent University Adana Training Hospital ( Site 0906)

Yüreğir, Adana, 01250, Turkey (Türkiye)

RECRUITING

Ege University Medicine of Faculty ( Site 0900)

Bornova, İzmir, 35100, Turkey (Türkiye)

RECRUITING

Hacettepe Universitesi-oncology hospital ( Site 0901)

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Ankara Bilkent Şehir Hastanesi. ( Site 0904)

Ankara, 06800, Turkey (Türkiye)

RECRUITING

Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 0902)

Istanbul, 34668, Turkey (Türkiye)

COMPLETED

Addenbrooke's Hospital ( Site 1309)

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

RECRUITING

Royal Free Hospital ( Site 1302)

London, England, NW3 2QG, United Kingdom

COMPLETED

The Beatson West of Scotland Cancer Centre ( Site 1308)

Glasgow, Glasgow City, G12 0YN, United Kingdom

RECRUITING

Hammersmith Hospital-Medical Oncology ( Site 1304)

London, London, City of, W12 OHS, United Kingdom

RECRUITING

Related Publications (1)

• Jimenez C, Andreassen M, Durand A, Moog S, Hendifar A, Welin S, Spada F, Sharma R, Wolin E, Ruether J, Garcia-Carbonero R, Fassnacht M, Capdevila J, Del Rivero J, Iliopoulos O, Huillard O, Jang R, Mai K, Artamonova E, Hallqvist A, Else T, Odeleye-Ajakaye A, Gozman A, Naik GS, Berruti A; LITESPARK-015 Investigators. Belzutifan for Advanced Pheochromocytoma or Paraganglioma. N Engl J Med. 2025 Nov 20;393(20):2012-2022. doi: 10.1056/NEJMoa2504964. Epub 2025 Oct 18.

  PMID: 41124218 RESULT

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma; Adenoma, Islet Cell; von Hippel-Lindau Disease

Interventions

belzutifan

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Adenoma; Neoplasms, Glandular and Epithelial; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; 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

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 11, 2021
• Study Start: August 12, 2021
• Primary Completion (Estimated): June 4, 2029
• Study Completion (Estimated): June 4, 2029
• Last Updated: May 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

CN (4); KR (2); TU (5); RU (5); NL (1); IL (2); IT (8); JP (6); PT (2); FR (6); NO (1); HU (1); SG (1); CA (2); AU (2); DE (5); GB (4); CL (2); ES (4); SE (4); US (14); DK (3)