Pheochromocytoma/ParagangliomaPhase 2NCT04924075
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)
A Phase 2 study testing Belzutifan in people with Pheochromocytoma/Paraganglioma and Pancreatic Neuroendocrine Tumor, run by Merck Sharp & Dohme LLC at 84 sites in 22 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Pheochromocytoma/Paraganglioma, Pancreatic Neuroendocrine Tumor, Von Hippel-Lindau Disease
- What is being tested?
- Belzutifan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 355 participants
- Where
- 84 sitesin 22 countries
- Study dates
- 12 Aug 2021to 18 Nov 2032
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Trial locations and contacts
84 sites in 22 countries. Contact the study team or a site near you to ask about taking part.
84 sites in 22 countries
United States14 sites, 10 recruiting
- Recruiting
University of Michigan ( Site 0126)
Ann Arbor, Michigan, 48109
Study Coordinator, 734-647-8902
- Recruiting
Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - Developmental Therapeutics ( Site 0108)
Baltimore, Maryland, 21287
Study Coordinator, 410-502-5140
- Recruiting
National Institutes of Health ( Site 0125)
Bethesda, Maryland, 20892
Study Coordinator, 240-858-3851
- Recruiting
Massachusetts General Hospital ( Site 0111)
Boston, Massachusetts, 02114
Study Coordinator, 617-724-4000
- Recruiting
Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0130)
Chicago, Illinois, 60611
Study Coordinator, 312-695-1310
- Recruiting
University of Texas MD Anderson Cancer Center ( Site 0112)
Houston, Texas, 77030
Study Coordinator, 713-792-2841
- Recruiting
University of Iowa ( Site 0104)
Iowa City, Iowa, 52242
Study Coordinator, 319-356-2148
- Recruiting
Cedars-Sinai Medical Center ( Site 0110)
Los Angeles, California, 90048
Study Coordinator, 310-967-2781
- Completed
SCRI Oncology Partners ( Site 7000)
Nashville, Tennessee, 37203
- Recruiting
Vanderbilt University Medical Center ( Site 0107)
Nashville, Tennessee, 37232
Study Coordinator, 800-811-8480
- Active, not recruiting
Icahn School of Medicine at Mount Sinai ( Site 0123)
New York, New York, 10029
- Active, not recruiting
Penn Medicine: University of Pennsylvania Health System-Heme/Onc ( Site 0127)
Philadelphia, Pennsylvania, 19104
- Active, not recruiting
Washington University-Internal Medicine/Oncology ( Site 0124)
St Louis, Missouri, 63110
- Recruiting
Northwestern Medicine Cancer Center - Warrenville ( Site 0134)
Warrenville, Illinois, 60555
Study Coordinator, 312-695-1310
Italy8 sites, 6 recruiting
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola ( Site 0708)
Bologna, 40138
Study Coordinator, + 39 051 2142708
- Recruiting
Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0701)
Brescia, 25123
Study Coordinator, +390303995410
- Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori-S.C. Oncologia Medica 2- Sarcomi ( Site 0709)
Milan, Lombardy, 20133
Study Coordinator, 0223902182
- Completed
Ospedale San Raffaele-Oncologia Medica ( Site 0705)
Milan, 20132
- Recruiting
Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroe ( Site 0700)
Milan, 20141
Study Coordinator, +390257489258
- Completed
University of Naples Federico II-Dipartimento di Medicina Clinica e Chirurgia ( Site 0704)
Naples, Campania, 80100
- Recruiting
Azienda Ospedaliero Universitaria Senese-U.O.C. Immunoterapia Oncologica ( Site 0706)
Siena, Tuscany, 53100
Study Coordinator, +39057758636
- Recruiting
Centro Ricerche Cliniche di Verona ( Site 0703)
Verona, 37134
Study Coordinator, +390458128131
France6 sites, 4 recruiting
- Recruiting
Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre ( Site 0407)
Le Kremlin-Bicêtre, Paris, 94270
Study Coordinator, 0145217453
- Recruiting
Hôpital Edouard Herriot-oncologie ( Site 0405)
Lyon, Auvergne-Rhône-Alpes, 69003
Study Coordinator, +33472119692
- Active, not recruiting
Institut Paoli-Calmettes-Oncology ( Site 0406)
Marseille, Bouches-du-Rhone, 13009
- Recruiting
Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0404)
Paris, 75014
Study Coordinator, +33158411439
- Recruiting
CHU Strasbourg-Hautepierre-Medecine Interne, Endocrinologie et Nutrition ( Site 0402)
Strasbourg, Alsace, 67098
Study Coordinator, +(0)3 88 12 75 93
- Active, not recruiting
Gustave Roussy ( Site 0403)
Villejuif, Île-de-France Region, 94805
Japan6 sites
- Active, not recruiting
National Cancer Center Hospital ( Site 1802)
Chuo-ku, Tokyo, 104-0045
- Active, not recruiting
Kyoto University Hospital ( Site 1806)
Kyoto, 606-8507
- Active, not recruiting
Kochi Medical School Hospital ( Site 1807)
Nankoku, Kochi, 783-8505
- Active, not recruiting
Hokkaido University Hospital ( Site 1800)
Sapporo, Hokkaido, 060-8648
- Active, not recruiting
Tokyo Women's Medical University Adachi Medical Center ( Site 1803)
Tokyo, 123-8558
- Active, not recruiting
Yokohama City University Hospital ( Site 1804)
Yokohama, Kanagawa, 236-0004
Germany5 sites, 4 recruiting
- Recruiting
Charité Universitaetsmedizin Berlin - Campus Mitte-Department of Endocrinology and Metabolism ( Site 0503)
Berlin, 10117
Study Coordinator, +4930450614303
- Recruiting
Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 0505)
Düsseldorf, North Rhine-Westphalia, 40225
Study Coordinator, +49 211 81 08030
- Recruiting
Universitaetsklinikum Freiburg ( Site 0504)
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Study Coordinator, +49761270-32613
- Completed
Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Department of Internal Medicine IV, Division ( Site 0501)
München, Bavaria, 80336
- Recruiting
Comprehensive Cancer Center Mainfranken-Div. of Endocrinology and Diabetes ( Site 0500)
Würzburg, Bavaria, 97080
Study Coordinator, 49-0931-20 13 90 21
Russia5 sites
- Active, not recruiting
Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 0801)
Moscow, Moscow, 115522
- Completed
Endocrinology Research Center of Rosmedtechnologies-Surgery ( Site 0809)
Moscow, Moscow, 117036
- Completed
Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov ( Site 0805)
Saint Petersburg, Leningradskaya Oblast', 190020
- Active, not recruiting
Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 0803)
Saint Petersburg, Leningradskaya Oblast', 198255
- Completed
GBUZ Republican Clinical Oncological Dispensary ( Site 0804)
Ufa, Baskortostan, Respublika, 450054
Turkey (Türkiye)5 sites, 4 recruiting
- Recruiting
Hacettepe Universitesi-oncology hospital ( Site 0901)
Ankara, 06230
Study Coordinator, 00903123052910
- Recruiting
Ankara Bilkent Şehir Hastanesi. ( Site 0904)
Ankara, 06800
Study Coordinator, 0090312 552 60 00
- Recruiting
Ege University Medicine of Faculty ( Site 0900)
Bornova, İzmir, 35100
Study Coordinator, 00902323903911
- Completed
Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 0902)
Istanbul, 34668
- Recruiting
Baskent University Adana Training Hospital ( Site 0906)
Yüreğir, Adana, 01250
Study Coordinator, +904449901
China4 sites
- Active, not recruiting
Peking University First Hospital-Urology ( Site 1900)
Beijing, Beijing Municipality, 100034
- Completed
West China Hospital of Sichuan University ( Site 1906)
Chengdu, Sichuan, 610041
- Active, not recruiting
Sun Yat-sen University Cancer Center ( Site 1905)
Guangzhou, Guangdong, 510060
- Active, not recruiting
Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1904)
Shanghai, Shanghai Municipality, 200001
Spain4 sites, 3 recruiting
- Recruiting
Hospital Universitari Vall d'Hebron ( Site 1100)
Barcelona, 08035
Study Coordinator, 34934894350
- Completed
MD Anderson Cancer Center-Oncology ( Site 1102)
Madrid, Madrid, Comunidad de, 28033
- Recruiting
Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1103)
Madrid, Madrid, Comunidad de, 28041
Study Coordinator, 34913908926
- Recruiting
Hospital Universitario Central de Asturias-Medical Oncology ( Site 1101)
Oviedo, Principality of Asturias, 33011
Study Coordinator, 34646662756
Sweden4 sites
- Active, not recruiting
Sahlgrenska Universitetssjukhuset-Department of Oncology CTU Clinical Trial Unit ( Site 1204)
Gothenburg, Västra Götaland County, 413 45
- Active, not recruiting
Skanes University Hospital Lund ( Site 1200)
Lund, Skåne County, 221 85
- Completed
Karolinska Universitetssjukhuset Solna ( Site 1202)
Stockholm, Stockholm County, 171 76
- Active, not recruiting
Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1201)
Uppsala, Uppsala County, 751 85
United Kingdom4 sites, 3 recruiting
- Recruiting
Addenbrooke's Hospital ( Site 1309)
Cambridge, Cambridgeshire, CB2 2QQ
Study Coordinator, +441223245151
- Recruiting
The Beatson West of Scotland Cancer Centre ( Site 1308)
Glasgow, Glasgow City, G12 0YN
Study Coordinator, +44 141 301 7055
- Active, not recruiting
Royal Free Hospital ( Site 1302)
London, England, NW3 2QG
- Recruiting
Hammersmith Hospital-Medical Oncology ( Site 1304)
London, London, City of, W12 OHS
Study Coordinator, 0208 383 3089
Denmark3 sites
- Active, not recruiting
Rigshospitalet ( Site 0304)
Copenhagen, Capital Region, 2100
- Active, not recruiting
Rigshospitalet-Department of Endocrinology ( Site 0303)
Copenhagen, Capital Region, 2100
- Active, not recruiting
Odense Universitetshospital ( Site 0302)
Odense C, Region Syddanmark, 5000
Australia2 sites, 2 recruiting
- Recruiting
The Royal Melbourne Hospital ( Site 1602)
Parkville, Victoria, 3050
Study Coordinator, +61 3 9342 7143
- Recruiting
Prince of Wales Hospital-Medical Oncology ( Site 1601)
Randwick, New South Wales, 2031
Study Coordinator, +61402035933
Canada2 sites, 2 recruiting
- Recruiting
Arthur J.E. Child Comprehensive Cancer Centre ( Site 0203)
Calgary, Alberta, T2N 5G2
Study Coordinator, 403-521-3165
- Recruiting
Princess Margaret Cancer Centre ( Site 0202)
Toronto, Ontario, M5G 2M9
Study Coordinator, 416-946-4501 x6508
Chile2 sites, 2 recruiting
- Recruiting
Fundación Arturo López Pérez ( Site 2200)
Santiago, Region M. de Santiago, 7500921
Study Coordinator, 56224205098
- Recruiting
Centro de Oncología de Precisión ( Site 2203)
Santiago, Region M. de Santiago, 7560908
Study Coordinator, +56225189885
Israel2 sites, 2 recruiting
- Recruiting
Sheba Medical Center-Institute of Endocrinology, Diabetes and Metabolism ( Site 1400)
Ramat Gan, 5262100
Study Coordinator, +97235303030
- Recruiting
Sourasky Medical Center ( Site 1401)
Tel Aviv, 6423906
Study Coordinator, +97236972062
Portugal2 sites, 2 recruiting
- Recruiting
START Lisbon - Hospital de Santa Maria ( Site 2601)
Lisbon, Lisbon District, 1649-035
Study Coordinator, +351 21 780 5000
- Recruiting
Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 2600)
Porto, 4200-072
Study Coordinator, (351) 225 084 000
South Korea2 sites
- Completed
Seoul National University Hospital ( Site 2001)
Jongno-gu, Seoul, 03080
- Active, not recruiting
Asan Medical Center ( Site 2000)
Songpa-gu, Seoul, 05505
Hungary1 site, 1 recruiting
- Recruiting
Semmelweis University-Belgyógyászati és Onkológiai Klinika Hematológia Osztály ( Site 0600)
Budapest, 1083
Study Coordinator, +3614591500
Netherlands1 site, 1 recruiting
- Recruiting
Universitair Medisch Centrum Utrecht ( Site 1530)
Utrecht, 3584 CX
Study Coordinator, 31887556308
Norway1 site
- Active, not recruiting
Oslo Universitetssykehus Radiumhospitalet ( Site 2400)
Oslo, 0424
Singapore1 site, 1 recruiting
- Recruiting
National Cancer Centre Singapore ( Site 1700)
Singapore, Central Singapore, 168583
Study Coordinator, +65 64368000
About this study
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
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
- Pheochromocytoma/Paraganglioma, Pancreatic Neuroendocrine Tumor, Von Hippel-Lindau Disease, Advanced Gastrointestinal Stromal Tumor, HIF-2α Mutated Cancers
- Being tested
- Belzutifan
- Keywords
- HIF-2α, Pheochromocytoma/paraganglioma, Pancreatic NET
- Medical subject headings
- Pheochromocytoma, Paraganglioma, Adenoma, Islet Cell, von Hippel-Lindau Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelzutifanDrug
Also called MK-6482, WELIREG™
Belzutifan, 120 mg, oral, once daily (QD) until progressive disease or discontinuation.
| Study group | Role | What they receive |
|---|---|---|
| Belzutifan | Experimental | Belzutifan, 120 mg, oral, once daily (QD) until progressive disease or discontinuation. Receives: Drug: Belzutifan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to approximately 5.5 years
Secondary outcomes (8)
Duration of Response (DOR) as Assessed by BICR
DOR is the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
Measured: Up to approximately 5.5 years
Time to Response (TTR) as Assessed by BICR
TTR is defined as the time from first dose of belzutifan to first documented evidence of CR or PR.
Measured: Up to approximately 5.5 years
Disease Control Rate (DCR) as Assessed by BICR
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).
Measured: Up to approximately 5.5 years
Progressive Free Survival (PFS) as Assessed by BICR
PFS is the time from first dose of belzutifan to the first documented PD or death from any cause, whichever occurs first.
Measured: Up to approximately 5.5 years
Overall Survival (OS)
OS is the time from first dose of belzutifan until death from any cause.
Measured: Up to approximately 5.5 years
Number of Participants Who Experience an Adverse Event (AE)
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.
Measured: Up to approximately 5.5 years
Number of Participants Who Discontinue Study Treatment Due to an AE
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.
Measured: Up to approximately 5.5 years
Time to Surgery (TTS)
TTS is defined as the time from the first dose of belzutifan to the first documented surgical intervention or tumor reduction procedure.
Measured: Up to approximately 5.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2021
- Study start12 Aug 2021
- Primary completion18 Nov 2032 (estimated)
- Study completion18 Nov 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pheochromocytoma/ParagangliomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 355 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04924075
- Sponsor's protocol ID
- 6482-015
- Other IDs
- MK-6482-015, PT2977, jRCT2011220024, 2023-504853-11-00, 2020-005028-13, 2023
- Status last verified
- Oct 2026
- First submitted
- 8 Jun 2021
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
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.
PubMed 41124218