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)

Phase 2

Recruiting

• Conditions: Pheochromocytoma/Paraganglioma; HIF-2α Mutated Cancers; Pancreatic Neuroendocrine Tumor; Von Hippel-Lindau Disease; Advanced Gastrointestinal Stromal Tumor
• Interventions: Drug: Belzutifan

• Registration Number: NCT04924075
• Lead Sponsor: Merck Sharp & Dohme LLC

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-08
• Study First Submitted QC: 2021-06-08
• Study First Posted: 2021-06-11
• Study Start: 2021-08-12
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-02
• Last Update Posted: 2025-05-06
• Primary Completion: 2029-06-04
• Study Completion: 2029-06-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 322

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)	Up to approximately 5.5 years	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Adverse Events (AEs)	Up to approximately 5.5 years	An AE is 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 is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time to Response (TTR) as Assessed by BICR	Up to approximately 5.5 years	TTR is defined as the time from first dose of belzutifan to first documented evidence of CR or PR.
Time to Surgery (TTS)	Up to approximately 5.5 years	TTS is defined as the time from the first dose of belzutifan to the first documented surgical intervention or tumor reduction procedure.
Progressive Free Survival (PFS) as Assessed by BICR	Up to approximately 5.5 years	PFS is the time from first dose of belzutifan to the first documented PD or death from any cause, whichever occurs first.
Number of Participants Discontinuing Study Drug due to an AE	Up to approximately 5.5 years	An adverse event (AE) is 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 is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinue study treatment due to an AE will be presented.
Duration of Response (DOR) as Assessed by BICR	Up to approximately 5.5 years	DOR is the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
Disease Control Rate (DCR) as Assessed by BICR	Up to approximately 5.5 years	Disease control is a confirmed CR, PR, or stable disease (SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study).
Overall Survival (OS)	Up to approximately 5.5 years	OS is the time from first dose of belzutifan until death from any cause.

Trial Locations

Locations (79)

Cedars-Sinai Medical Center ( Site 0110); 🇺🇸 Los Angeles, California, United States

West China Hospital of Sichuan University ( Site 1906); 🇨🇳 Cheng Du, Sichuan, China

Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0130); 🇺🇸 Chicago, Illinois, United States

University of Iowa ( Site 0104); 🇺🇸 Iowa City, Iowa, United States

Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - Developmental Therapeutics ( Site; 🇺🇸 Baltimore, Maryland, United States

National Institutes of Health ( Site 0125); 🇺🇸 Bethesda, Maryland, United States

Massachusetts General Hospital ( Site 0111); 🇺🇸 Boston, Massachusetts, United States

University of Michigan ( Site 0126); 🇺🇸 Ann Arbor, Michigan, United States

Washington University-Internal Medicine/Oncology ( Site 0124); 🇺🇸 Saint Louis, Missouri, United States

Icahn School of Medicine at Mount Sinai ( Site 0123); 🇺🇸 New York, New York, United States

Penn Medicine: University of Pennsylvania Health System-Heme/Onc ( Site 0127); 🇺🇸 Philadelphia, Pennsylvania, United States

SCRI Oncology Partners ( Site 7000); 🇺🇸 Nashville, Tennessee, United States

Vanderbilt University Medical Center ( Site 0107); 🇺🇸 Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center ( Site 0112); 🇺🇸 Houston, Texas, United States

Prince of Wales Hospital-Medical Oncology ( Site 1601); 🇦🇺 Randwick, New South Wales, Australia

The Royal Melbourne Hospital ( Site 1602); 🇦🇺 Parkville, Victoria, Australia

Arthur J.E. Child Comprehensive Cancer Centre ( Site 0203); 🇨🇦 Calgary, Alberta, Canada

Princess Margaret Cancer Centre ( Site 0202); 🇨🇦 Toronto, Ontario, Canada

FALP ( Site 2200); 🇨🇱 Santiago, Region M. De Santiago, Chile

Centro de Oncología de Precisión ( Site 2203); 🇨🇱 Santiago, Region M. De Santiago, Chile

Peking University First Hospital-Urology ( Site 1900); 🇨🇳 Beijing, Beijing, China

Sun Yat-sen University Cancer Center ( Site 1905); 🇨🇳 Guangzhou, Guangdong, China

Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1904); 🇨🇳 Shanghai, Shanghai, China

Rigshospitalet ( Site 0304); 🇩🇰 Copenhagen, Hovedstaden, Denmark

Rigshospitalet-Department of Endocrinology ( Site 0303); 🇩🇰 Copenhagen, Hovedstaden, Denmark

Odense Universitetshospital ( Site 0302); 🇩🇰 Odense C, Syddanmark, Denmark

CHU Strasbourg-Hautepierre-Medecine Interne, Endocrinologie et Nutrition ( Site 0402); 🇫🇷 Strasbourg, Alsace, France

Institut Paoli-Calmettes-Oncology ( Site 0406); 🇫🇷 Marseille, Bouches-du-Rhone, France

Gustave Roussy ( Site 0403); 🇫🇷 Villejuif, Ile-de-France, France

Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre ( Site 0407); 🇫🇷 Le Kremlin-Bicêtre, Paris, France

Hôpital Edouard Herriot-oncologie ( Site 0405); 🇫🇷 Lyon, Rhone-Alpes, France

Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0404); 🇫🇷 Paris, France

Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Department of Internal Medicine IV, Division (; 🇩🇪 München, Bayern, Germany

Comprehensive Cancer Center Mainfranken-Div. of Endocrinology and Diabetes ( Site 0500); 🇩🇪 Würzburg, Bayern, Germany

Universitaetsklinikum Freiburg ( Site 0504); 🇩🇪 Freiburg, Brandenburg, Germany

Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 0505); 🇩🇪 Düsseldorf, Nordrhein-Westfalen, Germany

Charité Universitaetsmedizin Berlin - Campus Mitte-Department of Endocrinology and Metabolism ( Site; 🇩🇪 Berlin, Germany

Semmelweis University-Belgyógyászati és Onkológiai Klinika Hematológia Osztály ( Site 0600); 🇭🇺 Budapest, Hungary

Sheba Medical Center-Institute of Endocrinology, Diabetes and Metabolism ( Site 1400); 🇮🇱 Ramat Gan, Israel

Sourasky Medical Center ( Site 1401); 🇮🇱 Tel Aviv, Israel

University of Naples Federico II-Dipartimento di Medicina Clinica e Chirurgia ( Site 0704); 🇮🇹 Naples, Campania, Italy

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

Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0701); 🇮🇹 Brescia, Italy

Ospedale San Raffaele-Oncologia Medica ( Site 0705); 🇮🇹 Milano, Italy

Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroe; 🇮🇹 Milano, Italy

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma ( Site 0703); 🇮🇹 Verona, Italy

Hokkaido University Hospital ( Site 1800); 🇯🇵 Sapporo, Hokkaido, Japan

Yokohama City University Hospital ( Site 1804); 🇯🇵 Yokohama-shi, Kanagawa, Japan

Kochi Medical School Hospital ( Site 1807); 🇯🇵 Nankoku, Kochi, Japan

National Cancer Center Hospital ( Site 1802); 🇯🇵 Chuo-ku, Tokyo, Japan

Kyoto University Hospital ( Site 1806); 🇯🇵 Kyoto, Japan

Tokyo Women's Medical University Adachi Medical Center ( Site 1803); 🇯🇵 Tokyo, Japan

Seoul National University Hospital ( Site 2001); 🇰🇷 Jongno-gu, Seoul, Korea, Republic of

Asan Medical Center ( Site 2000); 🇰🇷 Songpa-gu, Seoul, Korea, Republic of

Universitair Medisch Centrum Utrecht ( Site 1530); 🇳🇱 Utrecht, Netherlands

Oslo Universitetssykehus Radiumhospitalet ( Site 2400); 🇳🇴 Oslo, Norway

GBUZ Republican Clinical Oncological Dispensary ( Site 0804); 🇷🇺 Ufa, Baskortostan, Respublika, Russian Federation

Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov (; 🇷🇺 Saint Petersburg, Leningradskaya Oblast, Russian Federation

Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 0803); 🇷🇺 Saint Petersburg, Leningradskaya Oblast, Russian Federation

Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 0801); 🇷🇺 Moscow, Moskva, Russian Federation

Endocrinology Research Center of Rosmedtechnologies-Surgery ( Site 0809); 🇷🇺 Moscow, Moskva, Russian Federation

National Cancer Centre Singapore ( Site 1700); 🇸🇬 Singapore, Central Singapore, Singapore

Hospital Universitario Central de Asturias-Medical Oncology ( Site 1101); 🇪🇸 Oviedo, Asturias, Spain

MD Anderson Cancer Center-Oncology ( Site 1102); 🇪🇸 Madrid, Madrid, Comunidad De, Spain

Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1103); 🇪🇸 Madrid, Madrid, Comunidad De, Spain

Hospital Universitari Vall d'Hebron ( Site 1100); 🇪🇸 Barcelona, Spain

Skanes University Hospital Lund ( Site 1200); 🇸🇪 Lund, Skane Lan, Sweden

Karolinska Universitetssjukhuset Solna ( Site 1202); 🇸🇪 Stockholm, Stockholms Lan, Sweden

Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1201); 🇸🇪 Uppsala, Uppsala Lan, Sweden

Sahlgrenska Universitetssjukhuset-Department of Oncology CTU Clinical Trial Unit ( Site 1204); 🇸🇪 Gothenburg, Vastra Gotalands Lan, Sweden

Baskent University Adana Training Hospital ( Site 0906); 🇹🇷 Yuregir, Adana, Turkey

Ege University Medicine of Faculty ( Site 0900); 🇹🇷 Bornova, Izmir, Turkey

Hacettepe Universitesi-oncology hospital ( Site 0901); 🇹🇷 Ankara, Turkey

Ankara Bilkent Şehir Hastanesi. ( Site 0904); 🇹🇷 Ankara, Turkey

Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 0902); 🇹🇷 Istanbul, Turkey

Addenbrooke's Hospital ( Site 1309); 🇬🇧 Cambridge, Cambridgeshire, United Kingdom

Royal Free Hospital ( Site 1302); 🇬🇧 London, England, United Kingdom

The Beatson West of Scotland Cancer Centre ( Site 1308); 🇬🇧 Glasgow, Glasgow City, United Kingdom

Hammersmith Hospital-Medical Oncology ( Site 1304); 🇬🇧 London, London, City Of, United Kingdom