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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 · Merck Sharp & Dohme LLC
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Official title
A Phase 2 Study to Evaluate the Efficacy and Safety of Belzutifan (MK-6482, Formerly PT2977) Monotherapy in Participants With Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Advanced Solid Tumors With HIF-2α Related Genetic Alterations
About this study
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).
Eligibility criteria
The main inclusion criteria include but are not limited to the following: * 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 B1: 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 The main exclusion criteria include but are not limited to the following: * 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
Study design
Enrollment target: 355 participants
Allocation: na
Masking: none
Age groups: child, adult, older_adult
Timeline
Starts: 2021-08-12
Estimated completion: 2029-12-27
Last updated: 2026-07-20
Interventions
Drug: Belzutifan
Primary outcomes
  • Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) (Up to approximately 5.5 years)
Sponsor
Merck Sharp & Dohme LLC · industry
Contacts & investigators
ContactToll Free Number · contact · Trialsites@msd.com · 1-888-577-8839
InvestigatorMedical Director · study_director, Merck Sharp & Dohme LLC
All locations (84)
Cedars-Sinai Medical Center ( Site 0110)Recruiting
Los Angeles, California, United States
Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0130)Recruiting
Chicago, Illinois, United States
Northwestern Medicine Cancer Center - Warrenville ( Site 0134)Recruiting
Warrenville, Illinois, United States
University of Iowa ( Site 0104)Recruiting
Iowa City, Iowa, United States
Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - Developmental Therapeutics ( Site 0108)Recruiting
Baltimore, Maryland, United States
National Institutes of Health ( Site 0125)Recruiting
Bethesda, Maryland, United States
Massachusetts General Hospital ( Site 0111)Recruiting
Boston, Massachusetts, United States
University of Michigan ( Site 0126)Recruiting
Ann Arbor, Michigan, United States
Washington University-Internal Medicine/Oncology ( Site 0124)Active Not Recruiting
St Louis, Missouri, United States
Icahn School of Medicine at Mount Sinai ( Site 0123)Active Not Recruiting
New York, New York, United States
Penn Medicine: University of Pennsylvania Health System-Heme/Onc ( Site 0127)Active Not Recruiting
Philadelphia, Pennsylvania, United States
SCRI Oncology Partners ( Site 7000)Recruiting
Nashville, Tennessee, United States
Vanderbilt University Medical Center ( Site 0107)Recruiting
Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center ( Site 0112)Recruiting
Houston, Texas, United States
Prince of Wales Hospital-Medical Oncology ( Site 1601)Recruiting
Randwick, New South Wales, Australia
The Royal Melbourne Hospital ( Site 1602)Recruiting
Parkville, Victoria, Australia
Arthur J.E. Child Comprehensive Cancer Centre ( Site 0203)Recruiting
Calgary, Alberta, Canada
Princess Margaret Cancer Centre ( Site 0202)Recruiting
Toronto, Ontario, Canada
FALP ( Site 2200)Recruiting
Santiago, Region M. de Santiago, Chile
Centro de Oncología de Precisión ( Site 2203)Recruiting
Santiago, Region M. de Santiago, Chile
Peking University First Hospital-Urology ( Site 1900)Active Not Recruiting
Beijing, Beijing Municipality, China
Sun Yat-sen University Cancer Center ( Site 1905)Active Not Recruiting
Guangzhou, Guangdong, China
Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1904)Active Not Recruiting
Shanghai, Shanghai Municipality, China
West China Hospital of Sichuan University ( Site 1906)Completed
Chengdu, Sichuan, China
Rigshospitalet ( Site 0304)Recruiting
Copenhagen, Capital Region, Denmark
Rigshospitalet-Department of Endocrinology ( Site 0303)Recruiting
Copenhagen, Capital Region, Denmark
Odense Universitetshospital ( Site 0302)Recruiting
Odense, Region Syddanmark, Denmark
CHU Strasbourg-Hautepierre-Medecine Interne, Endocrinologie et Nutrition ( Site 0402)Recruiting
Strasbourg, Alsace, France
Hôpital Edouard Herriot-oncologie ( Site 0405)Recruiting
Lyon, Auvergne-Rhône-Alpes, France
Institut Paoli-Calmettes-Oncology ( Site 0406)Active Not Recruiting
Marseille, Bouches-du-Rhone, France
Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre ( Site 0407)Recruiting
Le Kremlin-Bicêtre, Paris, France
Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0404)Recruiting
Paris, France
Gustave Roussy ( Site 0403)Recruiting
Villejuif, Île-de-France Region, France
Universitaetsklinikum Freiburg ( Site 0504)Recruiting
Freiburg im Breisgau, Baden-Wurttemberg, Germany
Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Department of Internal Medicine IV, Division ( Site 0501)Completed
München, Bavaria, Germany
Comprehensive Cancer Center Mainfranken-Div. of Endocrinology and Diabetes ( Site 0500)Recruiting
Würzburg, Bavaria, Germany
Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 0505)Recruiting
Düsseldorf, North Rhine-Westphalia, Germany
Charité Universitaetsmedizin Berlin - Campus Mitte-Department of Endocrinology and Metabolism ( Site 0503)Recruiting
Berlin, Germany
Semmelweis University-Belgyógyászati és Onkológiai Klinika Hematológia Osztály ( Site 0600)Recruiting
Budapest, Hungary
Sheba Medical Center-Institute of Endocrinology, Diabetes and Metabolism ( Site 1400)Recruiting
Ramat Gan, Israel
Sourasky Medical Center ( Site 1401)Recruiting
Tel Aviv, Israel
University of Naples Federico II-Dipartimento di Medicina Clinica e Chirurgia ( Site 0704)Completed
Naples, Campania, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori-S.C. Oncologia Medica 2- Sarcomi ( Site 0709)Recruiting
Milan, Lombardy, Italy
Azienda Ospedaliero Universitaria Senese-U.O.C. Immunoterapia Oncologica ( Site 0706)Recruiting
Siena, Tuscany, Italy
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola ( Site 0708)Recruiting
Bologna, Italy
Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0701)Recruiting
Brescia, Italy
Ospedale San Raffaele-Oncologia Medica ( Site 0705)Completed
Milan, Italy
Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroe ( Site 0700)Recruiting
Milan, Italy
Centro Ricerche Cliniche di Verona ( Site 0703)Recruiting
Verona, Italy
Hokkaido University Hospital ( Site 1800)Active Not Recruiting
Sapporo, Hokkaido, Japan
Yokohama City University Hospital ( Site 1804)Active Not Recruiting
Yokohama, Kanagawa, Japan
Kochi Medical School Hospital ( Site 1807)Active Not Recruiting
Nankoku, Kochi, Japan
National Cancer Center Hospital ( Site 1802)Active Not Recruiting
Chuo-ku, Tokyo, Japan
Kyoto University Hospital ( Site 1806)Active Not Recruiting
Kyoto, Japan
Tokyo Women's Medical University Adachi Medical Center ( Site 1803)Active Not Recruiting
Tokyo, Japan
Universitair Medisch Centrum Utrecht ( Site 1530)Recruiting
Utrecht, Netherlands
Oslo Universitetssykehus Radiumhospitalet ( Site 2400)Recruiting
Oslo, Norway
START Lisbon - Hospital de Santa Maria ( Site 2601)Recruiting
Lisbon, Lisbon District, Portugal
Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 2600)Recruiting
Porto, Portugal
GBUZ Republican Clinical Oncological Dispensary ( Site 0804)Completed
Ufa, Baskortostan, Respublika, Russia
Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov ( Site 0805)Completed
Saint Petersburg, Leningradskaya Oblast', Russia
Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 0803)Active Not Recruiting
Saint Petersburg, Leningradskaya Oblast', Russia
Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 0801)Active Not Recruiting
Moscow, Moscow, Russia
Endocrinology Research Center of Rosmedtechnologies-Surgery ( Site 0809)Completed
Moscow, Moscow, Russia
National Cancer Centre Singapore ( Site 1700)Recruiting
Singapore, Central Singapore, Singapore
Seoul National University Hospital ( Site 2001)Recruiting
Jongno-gu, Seoul, South Korea
Asan Medical Center ( Site 2000)Recruiting
Songpa-gu, Seoul, South Korea
MD Anderson Cancer Center-Oncology ( Site 1102)Completed
Madrid, Madrid, Comunidad de, Spain
Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1103)Recruiting
Madrid, Madrid, Comunidad de, Spain
Hospital Universitario Central de Asturias-Medical Oncology ( Site 1101)Recruiting
Oviedo, Principality of Asturias, Spain
Hospital Universitari Vall d'Hebron ( Site 1100)Recruiting
Barcelona, Spain
Skanes University Hospital Lund ( Site 1200)Recruiting
Lund, Skåne County, Sweden
Karolinska Universitetssjukhuset Solna ( Site 1202)Completed
Stockholm, Stockholm County, Sweden
Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1201)Recruiting
Uppsala, Uppsala County, Sweden
Sahlgrenska Universitetssjukhuset-Department of Oncology CTU Clinical Trial Unit ( Site 1204)Recruiting
Gothenburg, Västra Götaland County, Sweden
Baskent University Adana Training Hospital ( Site 0906)Recruiting
Yüreğir, Adana, Turkey (Türkiye)
Ege University Medicine of Faculty ( Site 0900)Recruiting
Bornova, İzmir, Turkey (Türkiye)
Hacettepe Universitesi-oncology hospital ( Site 0901)Recruiting
Ankara, Turkey (Türkiye)
Ankara Bilkent Şehir Hastanesi. ( Site 0904)Recruiting
Ankara, Turkey (Türkiye)
Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 0902)Completed
Istanbul, Turkey (Türkiye)
Addenbrooke's Hospital ( Site 1309)Recruiting
Cambridge, Cambridgeshire, United Kingdom
Royal Free Hospital ( Site 1302)Active Not Recruiting
London, England, United Kingdom
The Beatson West of Scotland Cancer Centre ( Site 1308)Recruiting
Glasgow, Glasgow City, United Kingdom
Hammersmith Hospital-Medical Oncology ( Site 1304)Recruiting
London, London, City of, United Kingdom
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) · TrialPath