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)

April 10, 2024 updated by: Merck Sharp & Dohme LLC

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 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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

322

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Recruiting
        • Prince of Wales Hospital-Medical Oncology ( Site 1601)
        • Contact:
          • Study Coordinator
          • Phone Number: +61402035933
    • Victoria
      • Parkville, Victoria, Australia, 3050
        • Recruiting
        • The Royal Melbourne Hospital ( Site 1602)
        • Contact:
          • Study Coordinator
          • Phone Number: +61 3 9342 7143
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Recruiting
        • Tom Baker Cancer Center ( Site 0203)
        • Contact:
          • Study Coordinator
          • Phone Number: 403-521-3165
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Princess Margaret Cancer Centre ( Site 0202)
        • Contact:
          • Study Coordinator
          • Phone Number: 416-946-4501 Ext 6508
  • China
    • Beijing
      • Beijing, Beijing, China, 100034
        • Active, not recruiting
        • Peking University First Hospital-Urology ( Site 1900)
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Active, not recruiting
        • Sun Yat-sen University Cancer Center ( Site 1905)
    • Shanghai
      • Shanghai, Shanghai, China
        • Active, not recruiting
        • Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 1904)
    • Sichuan
      • Cheng Du, Sichuan, China, 610041
        • Recruiting
        • West China Hospital of Sichuan University ( Site 1906)
        • Contact:
          • Study Coordinator
          • Phone Number: +86 18608033400
  • Denmark
    • Hovedstaden
      • Copenhagen, Hovedstaden, Denmark, 2100
        • Recruiting
        • Rigshospitalet-Department of Endocrinology ( Site 0303)
        • Contact:
          • Study Coordinator
          • Phone Number: 35457562
      • Copenhagen, Hovedstaden, Denmark, 2100
        • Recruiting
        • Rigshospitalet ( Site 0304)
        • Contact:
          • Study Coordinator
          • Phone Number: +45 35456353
    • Syddanmark
      • Odense, Syddanmark, Denmark, 5000
        • Recruiting
        • Odense Universitetshospital ( Site 0302)
        • Contact:
          • Study Coordinator
          • Phone Number: +45 66 11 33 33
  • France
      • Paris, France, 75014
        • Recruiting
        • Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0404)
        • Contact:
          • Study Coordinator
          • Phone Number: +33158411439
    • Alsace
      • Strasbourg, Alsace, France, 67098
        • Recruiting
        • CHU Strasbourg-Hautepierre-Medecine Interne, Endocrinologie et Nutrition ( Site 0402)
        • Contact:
          • Study Coordinator
          • Phone Number: +(0)3 88 12 75 93
    • Bouches-du-Rhone
      • Marseille, Bouches-du-Rhone, France, 13009
        • Recruiting
        • Institut Paoli-Calmettes-Oncology ( Site 0406)
        • Contact:
          • Study Coordinator
          • Phone Number: 0491223302
    • Ile-de-France
      • Villejuif, Ile-de-France, France, 94800
        • Recruiting
        • Gustave Roussy ( Site 0403)
        • Contact:
          • Study Coordinator
          • Phone Number: +33142114211
    • Paris
      • Le Kremlin-Bicêtre, Paris, France, 94270
        • Recruiting
        • Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre ( Site 0407)
        • Contact:
          • Study Coordinator
          • Phone Number: 003345212380
    • Rhone-Alpes
      • Lyon, Rhone-Alpes, France, 69003
        • Recruiting
        • Hôpital Edouard Herriot-oncologie ( Site 0405)
        • Contact:
          • Study Coordinator
          • Phone Number: +33472119692
  • Germany
      • Berlin, Germany, 10117
        • Recruiting
        • Charité Universitaetsmedizin Berlin - Campus Mitte-Department of Endocrinology and Metabolism ( Site
        • Contact:
          • Study Coordinator
          • Phone Number: +4930450614303
    • Baden-Wurttemberg
      • Freiburg, Baden-Wurttemberg, Germany, 79106
        • Recruiting
        • Universitaetsklinikum Freiburg ( Site 0504)
        • Contact:
          • Study Coordinator
          • Phone Number: +49761270-32613
    • Bayern
      • München, Bayern, Germany, 80336
        • Recruiting
        • Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Department of Internal Medicine IV, Division (
        • Contact:
          • Study Coordinator
          • Phone Number: +4989440052221
      • Würzburg, Bayern, Germany, 97080
        • Recruiting
        • Comprehensive Cancer Center Mainfranken-Div. of Endocrinology and Diabetes ( Site 0500)
        • Contact:
          • Study Coordinator
          • Phone Number: +49-(0)931-20 13 90 21
  • Hungary
      • Budapest, Hungary, 1083
        • Recruiting
        • Semmelweis University-Belgyógyászati és Onkológiai Klinika Hematológia Osztály ( Site 0600)
        • Contact:
          • Study Coordinator
          • Phone Number: +3614591500
  • Israel
      • Ramat Gan, Israel, 5262100
        • Recruiting
        • Sheba Medical Center-Institute of Endocrinology, Diabetes and Metabolism ( Site 1400)
        • Contact:
          • Study Coordinator
          • Phone Number: +972506844706
      • Tel Aviv, Israel, 6423906
        • Recruiting
        • Sourasky Medical Center ( Site 1401)
        • Contact:
          • Study Coordinator
          • Phone Number: 97236973082
  • Italy
      • Brescia, Italy, 25123
        • Recruiting
        • Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 0701)
        • Contact:
          • Study Coordinator
          • Phone Number: +390303995410
      • Milano, Italy, 20141
        • Recruiting
        • Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroe
        • Contact:
          • Study Coordinator
          • Phone Number: +390257489258
      • Verona, Italy, 37134
        • Recruiting
        • Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma ( Site 0703)
        • Contact:
          • Study Coordinator
          • Phone Number: +390458128131
    • Campania
      • Naples, Campania, Italy, 80100
        • Completed
        • University of Naples Federico II-Dipartimento di Medicina Clinica e Chirurgia ( Site 0704)
    • Lombardia
      • Milano, Lombardia, Italy, 20132
        • Recruiting
        • Ospedale San Raffaele-Oncologia Medica ( Site 0705)
        • Contact:
          • Study Coordinator
          • Phone Number: +39 0226435789
  • Japan
      • Kyoto, Japan
        • Active, not recruiting
        • Kyoto University Hospital ( Site 1806)
      • Tokyo, Japan, 123-8558
        • Active, not recruiting
        • Tokyo Women's Medical University Adachi Medical Center ( Site 1803)
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8648
        • Active, not recruiting
        • Hokkaido University Hospital ( Site 1800)
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 236-0004
        • Active, not recruiting
        • Yokohama City University Hospital-Department of Urology ( Site 1804)
    • Kochi
      • Nankoku, Kochi, Japan, 783-8505
        • Active, not recruiting
        • Kochi Medical School Hospital ( Site 1807)
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • Active, not recruiting
        • National Cancer Center Hospital ( Site 1802)
  • Netherlands
      • Utrecht, Netherlands, 3584 CX
        • Recruiting
        • Universitair Medisch Centrum Utrecht ( Site 1530)
        • Contact:
          • Study Coordinator
          • Phone Number: 31887556308
  • Russian Federation
    • Baskortostan, Respublika
      • Ufa, Baskortostan, Respublika, Russian Federation, 450054
        • Suspended
        • GBUZ Republican Clinical Oncological Dispensary ( Site 0804)
    • Leningradskaya Oblast
      • Saint Petersburg, Leningradskaya Oblast, Russian Federation, 198255
        • Suspended
        • Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 0803)
      • Saint Petersburg, Leningradskaya Oblast, Russian Federation, 190020
        • Completed
        • Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov (
    • Moskva
      • Moscow, Moskva, Russian Federation, 115478
        • Suspended
        • Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 0801)
      • Moscow, Moskva, Russian Federation, 117036
        • Completed
        • Endocrinology Research Center of Rosmedtechnologies-Surgery ( Site 0809)
  • Singapore
    • Central Singapore
      • Singapore, Central Singapore, Singapore, 168583
        • Recruiting
        • National Cancer Centre Singapore ( Site 1700)
        • Contact:
          • Study Coordinator
          • Phone Number: 64368000
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall d'Hebron ( Site 1100)
        • Contact:
          • Study Coordinator
          • Phone Number: 34934894350
    • Asturias
      • Oviedo, Asturias, Spain, 33011
        • Recruiting
        • Hospital Universitario Central de Asturias-Medical Oncology ( Site 1101)
        • Contact:
          • Study Coordinator
          • Phone Number: 34646662756
    • Madrid, Comunidad De
      • Madrid, Madrid, Comunidad De, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1103)
        • Contact:
          • Study Coordinator
          • Phone Number: 34913908926
      • Madrid, Madrid, Comunidad De, Spain, 28033
        • Completed
        • MD Anderson Cancer Center-Oncology ( Site 1102)
  • Sweden
    • Skane Lan
      • Lund, Skane Lan, Sweden, 221 85
        • Recruiting
        • Skanes University Hospital Lund ( Site 1200)
        • Contact:
          • Study Coordinator
          • Phone Number: +4646171000
    • Stockholms Lan
      • Stockholm, Stockholms Lan, Sweden, 171 76
        • Completed
        • Karolinska Universitetssjukhuset Solna ( Site 1202)
    • Uppsala Lan
      • Uppsala, Uppsala Lan, Sweden, 751 85
        • Recruiting
        • Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1201)
        • Contact:
          • Study Coordinator
          • Phone Number: +46186110000
    • Vastra Gotalands Lan
      • Gothenburg, Vastra Gotalands Lan, Sweden, 413 45
        • Recruiting
        • Sahlgrenska Universitetssjukhuset-Department of Oncology CTU Clinical Trial Unit ( Site 1204)
        • Contact:
          • Study Coordinator
          • Phone Number: +46313421000
  • Turkey
      • Ankara, Turkey, 06230
        • Recruiting
        • Hacettepe Universitesi-oncology hospital ( Site 0901)
        • Contact:
          • Study Coordinator
          • Phone Number: 00903123052910
      • Ankara, Turkey, 06800
        • Recruiting
        • Ankara Bilkent Şehir Hastanesi. ( Site 0904)
        • Contact:
          • Study Coordinator
          • Phone Number: 0090312 552 60 00
      • Istanbul, Turkey, 34668
        • Recruiting
        • Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 0902)
        • Contact:
          • Study Coordinator
          • Phone Number: 00905324167355
    • Izmir
      • Bornova, Izmir, Turkey, 35100
        • Recruiting
        • Ege University Medicine of Faculty ( Site 0900)
        • Contact:
          • Study Coordinator
          • Phone Number: 00902323903911
  • United Kingdom
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ
        • Recruiting
        • Addenbrooke's Hospital ( Site 1309)
        • Contact:
          • Study Coordinator
          • Phone Number: +441223245151
    • England
      • London, England, United Kingdom, NW32QG
        • Active, not recruiting
        • Royal Free Hospital ( Site 1302)
    • Glasgow City
      • Glasgow, Glasgow City, United Kingdom, G12 0YN
        • Recruiting
        • The Beatson West of Scotland Cancer Centre ( Site 1308)
        • Contact:
          • Study Coordinator
          • Phone Number: +44 141 301 7055
    • London, City Of
      • London, London, City Of, United Kingdom, W12 OHS
        • Recruiting
        • Hammersmith Hospital-Medical Oncology ( Site 1304)
        • Contact:
          • Study Coordinator
          • Phone Number: 0208 383 3089
  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center ( Site 0110)
        • Contact:
          • Study Coordinator
          • Phone Number: 310-967-2781
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa ( Site 0104)
        • Contact:
          • Study Coordinator
          • Phone Number: 319-356-2148
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - Developmental Therapeutics ( Site
        • Contact:
          • Study Coordinator
          • Phone Number: 410-502-5140
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital ( Site 0111)
        • Contact:
          • Study Coordinator
          • Phone Number: 617-724-4000
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan ( Site 0126)
        • Contact:
          • Study Coordinator
          • Phone Number: 734-647-8902
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University-Internal Medicine/Oncology ( Site 0124)
        • Contact:
          • Study Coordinator
          • Phone Number: 314-747-6268
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai ( Site 0123)
        • Contact:
          • Study Coordinator
          • Phone Number: 212-824-2385
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Penn Medicine: University of Pennsylvania Health System-Heme/Onc ( Site 0127)
        • Contact:
          • Study Coordinator
          • Phone Number: 215-615-1725
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center ( Site 0107)
        • Contact:
          • Study Coordinator
          • Phone Number: 800-811-8480
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas MD Anderson Cancer Center ( Site 0112)
        • Contact:
          • Study Coordinator
          • Phone Number: 713-792-2841

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Cohort A1: Pheochromocytoma/Paraganglioma (PPGL)

- Has documented histopathological diagnosis (local report) of pheochromocytoma or paraganglioma Note: Participants are allowed to receive therapy in first line where a satisfactory treatment option does not exist and if participants are not candidates for systemic chemotherapy or have refused such therapy. There is no limit on number of prior systemic therapies.

Locoregional therapies or adjuvant/neoadjuvant therapies are not considered a line of prior systemic therapy

  • Has locally advanced or metastatic disease that is not amenable to surgery or curative intent treatment
  • Has adequately controlled blood pressure defined as blood pressure ≤150/90 mm Hg (≤135/85 mm Hg for adolescents) and with no change in antihypertensive medications (for participants with concomitant hypertension) for at least 2 weeks prior to start of study treatment.

Cohort A2: Pancreatic Neuroendocrine Tumor (pNET)

  • Has documented histopathological or cytopathological diagnosis (local report) of well-differentiated, low, or intermediate grade (G1 or G2 pNET per 2017 World Health Organization (WHO) classification and grading) pNET.

  • Has locally advanced disease or metastatic disease that is:

    1. Not amenable for surgery, radiation, locoregional therapies or combination modality of such treatments with curative intent.
    2. Experienced disease progression on or after at least 1 line of prior systemic therapy that includes an approved targeted agent such as everolimus or sunitinib. Participants who have received >3 prior systemic therapies will be capped to ≤20% of the cohort.

Note: Chemoembolization/radiofrequency ablation/locoregional therapies, neoadjuvant/adjuvant treatments, or somatostatin analog monotherapy or interferon monotherapy will not count as 1 line of prior systemic therapy.

Cohorts A1, A2 and PPGL/pNET participants from Cohort D

  • Has disease progression within the past 12 months from Screening.

  • Has measurable disease per RECIST 1.1 by computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by local site investigator/radiology assessment and verified by BICR.

    1. Irradiated lesions or lesions treated with locoregional therapies should not be used as target lesions unless they clearly demonstrate growth since completion of radiation.
    2. Metastatic lesions situated in the brain are not considered measurable and should be considered nontarget lesions.
    3. Only lesions of the primary indication for the cohort may be evaluated for measurability; other neoplastic lesions will be documented by the investigator and this information provided to the independent reviewers to ensure that such lesions are not included in the RECIST assessment.
    4. Participants who are adolescents (12-17 years of age) need to have a body weight of 40 kilograms (kg) or more.

Cohort B1: von Hippel-Lindau (VHL) Disease-Associated Tumors

  • Have a diagnosis of VHL disease as determined by a germline test (documented germline VHL gene alteration) locally and/or clinical diagnosis.
  • Have at least 1 measurable PPGL or pNET per RECIST 1.1 by CT or MRI as assessed by local site investigator/radiology assessment and verified by BICR.
  • Participants from China or Japan defined as participants of Chinese or Japanese origin residing in mainland China or Japan respectively at the time of Screening, must have at least 1 measurable RCC or PPGL or pNET per RECIST 1.1 as assessed by local site investigator/radiology assessment and verified by BICR.
  • Must be ≥18 years of age.

For Cohort B1 participants with PPGL

  • Must not have pheochromocytoma >5 cm or paraganglioma >4 cm that requires immediate surgery.
  • Have adequately controlled blood pressure defined as blood pressure ≤150/90 mm Hg and with no change in antihypertensive medications (for participants with concomitant hypertension) for at least 2 weeks prior to start of study treatment.
  • Must not have Metastatic or locally advanced, unresectable PPGL.
  • Presence of concomitant VHL disease-associated tumors is permitted as long as they do not require immediate surgery or intervention.

For Cohort B1 participants with pNET:

  • Must not have lesion(s) located in the head of the pancreas must be >2 cm that requires immediate surgery.
  • Must not have lesion(s) located in the body or tail of the pancreas must be >3 cm that requires immediate surgery.
  • Must not have locally advanced, unresectable or metastatic pNET.
  • Presence of concomitant VHL disease-associated tumors is permitted as long as they do not require immediate surgery or intervention.

For Cohort B1 participants with renal cell carcinoma (RCC):

  • Must not have lesion(s) >3 cm that requires immediate surgery.
  • Must not have metastatic RCC.
  • Presence of concomitant VHL disease-associated tumors is permitted as long as they do not require immediate surgery or intervention.

For Cohort C participants with GIST (wt):

  • Has documented histopathological diagnosis of GIST.
  • Local test report documenting the absence of sensitizing mutations in both platelet derived growth factor receptor alpha (PDGFRA) and receptor tyrosine kinase (c-KIT).
  • Has locally advanced or metastatic disease that is not amenable to surgery or curative intent treatment.

For Cohort D participants with advanced solid tumors with HIF-2α related genetic alterations:

  • Local test report documenting germline or somatic mutations in at least one of the HIF-2α related genes.
  • Has locally advanced or metastatic solid tumor that is not amenable to surgery or curative intent treatment.
  • Has progressed on/after standard therapy for advanced/metastatic disease.

  • Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of study intervention:

    1. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR
    2. Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below:

    i. Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman/women of childbearing potential (WOCBP) who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.

  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

    1. Is not a WOCBP OR
    2. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), for at least 30 days after the last dose of study intervention.
  • Submit an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (not previously irradiated). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue if the lesion is accessible and a biopsy is not clinically contraindicated.

Note: If participant has only 1 measurable lesion per RECIST 1.1, the biopsy specimen should be obtained from a nontarget lesion or archival tissue. Bone biopsies should not be submitted.

  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 7 days of treatment initiation.
  • Has adequate organ function.
  • Has a life expectancy of at least 3 months.

Exclusion Criteria:

  • Is unable to swallow orally administered medication or has a disorder that might affect the absorption of belzutifan.
  • Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years with the following exceptions:

Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.

  • Participants with history of VHL disease (germline VHL mutation documented by a local test report or with clinical diagnosis) will be permitted provided concurrent lesions (other than the tumor type being assessed such as PPGL for Cohort A1 and pNET for Cohort A2) are localized without immediate need for intervention. Cohort D participants with VHL disease will not be eligible.
  • Prior history of surgical resection(s) for concurrent localized VHL disease-associated tumors is allowed provided there is no history of metastatic disease from concurrent tumors; history of systemic therapy for concurrent tumors will be exclusionary.
  • Participants with history of other genetic syndromes (such as those with succinate dehydrogenase subunit genes (SDHx) germline mutation or multiple endocrine neoplasia/MEN) will be allowed provided concurrent tumors (outside of the organ affected in Cohort A1, Cohort A2, C and D respectively) are localized and do not require immediate intervention; history of metastatic disease in concurrent tumors or history of systemic therapy for concurrent tumors will be exclusionary.
  • Cohort B1 participants with concomitant central nervous system (CNS) hemangioblastoma must not require immediate surgery or intervention and must not be at risk of imminent neurological complications.
  • Cohort B1 participants with concomitant retinal angiomas/retinal hemangioblastomas must not require immediate intervention.
  • Cohort B1 participants with any concomitant tumors must not require immediate surgery or intervention.
  • For Cohort B1 participants, history of any anticancer systemic therapy (including investigational agents) for any VHL disease-associated tumor or history of metastatic disease from any VHL disease-associated tumor or other non-VHL disease-related tumor(s) will be exclusionary.
  • Has known CNS metastases and/or carcinomatous meningitis.
  • Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction, or arterial bypass (CABG) or percutaneous transluminal coronary angioplasty (PTCA) ≤6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Concurrent uncontrolled hypertension defined as blood pressure >150/90 mm mercury (Hg) despite optimal antihypertensive medications within 2 weeks prior to the first dose of study treatment.

Note: Medically controlled arrhythmia stable on medication is permitted.

  • Has any of the following: A pulse oximeter reading <92% at rest, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
  • Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
  • Has had major surgery ≤4 weeks prior to first dose of study intervention.
  • Has received prior treatment (except somatostatin analogs for pNET participants) with chemotherapy, targeted therapy, biologics or other investigational therapy within the past 4 weeks of first dose of study intervention.
  • Has received prior locoregional therapies or radiation within the past 4 weeks of first dose of study intervention.
  • Has received prior treatment with Peptide Receptor Radionuclide Therapy (PRRT)/radionuclide therapy (such as 177Lu-Dotatate) or other radiopharmaceutical therapy within the past 12 weeks from Screening for participants with pNET.
  • Has received meta-iodobenzylguanidine (MIBG) therapy or other radiopharmaceutical therapy within the past 12 weeks from Screening for participants with PPGL.
  • Has received prior treatment with any HIF-2α inhibitor (including belzutifan).
  • Has a known hypersensitivity to the study treatment and/or any of its excipients.
  • Has toxicities from prior locoregional or systemic or any other therapies that is not recovered to Common Terminology Criteria for Adverse Events (CTCAE) ≤Grade 1 (with the exception of alopecia).
  • Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), or recombinant Erythropoietin (EPO) ≤28 days prior to the first dose of study intervention.
  • Is currently receiving strong inhibitors of Cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study.
  • Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study.
  • Is currently enrolled in and receiving study therapy, was enrolled in a study of an investigational agent, and received study therapy or used an investigational device within 4 weeks (28 days) of the first dose of study intervention.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known history of hepatitis B or known active hepatitis C (HCV) infection.

  • For Cohort A2, has a tumor histology consistent with poorly differentiated pNET, neuroendocrine carcinoma, or neuroendocrine tumor (NET) of nonpancreatic origin.

    1. Poorly differentiated or high grade pancreatic pNET or pancreatic neuroendocrine carcinoma; mixed adenoneuroendocrine carcinoma of the pancreas or concurrent pancreatic ductal adenocarcinoma will not be allowed.
    2. Neuroendocrine tumor of nonpancreatic origin such as gastrointestinal, lung/thoracic, unknown primary, or other organs (including adenocarcinoid/goblet cell carcinoid/small cell carcinoma/large cell carcinoma). Note: Neuroendocrine carcinoma of any origin is exclusionary.
  • For Cohort A2, participants who have uncontrolled symptoms from functional pNETs at study entry.
  • Has had an allogenic tissue/solid organ transplant.
  • For Cohort B1 participants, metastatic disease identified at Screening.
  • For Cohort C and GIST participants, clinically significant active bleeding (such as gastrointestinal [GI] bleeding), perforation, obstruction, and other disease-related complications, requiring emergency surgery.
  • For Cohort D participants, VHL disease is exclusionary.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Belzutifan
Belzutifan, 120 mg, oral, once daily (QD) until progressive disease or discontinuation.
Drug: Belzutifan
Belzutifan, 120 mg, oral, once daily (QD) until progressive disease or discontinuation.
Other Names:
  • MK-6482
  • WELIREG™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)
Time Frame: 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.
Up to approximately 5.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR) as Assessed by BICR
Time Frame: 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.
Up to approximately 5.5 years
Time to Response (TTR) as Assessed by BICR
Time Frame: 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.
Up to approximately 5.5 years
Disease Control Rate (DCR) as Assessed by BICR
Time Frame: 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).
Up to approximately 5.5 years
Progressive Free Survival (PFS) as Assessed by BICR
Time Frame: 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.
Up to approximately 5.5 years
Overall Survival (OS)
Time Frame: Up to approximately 5.5 years
OS is the time from first dose of belzutifan until death from any cause.
Up to approximately 5.5 years
Number of Participants Experiencing Adverse Events (AEs)
Time Frame: 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.
Up to approximately 5.5 years
Number of Participants Discontinuing Study Drug due to an AE
Time Frame: 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.
Up to approximately 5.5 years
Time to Surgery (TTS)
Time Frame: 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.
Up to approximately 5.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 12, 2021

Primary Completion (Estimated)

February 26, 2027

Study Completion (Estimated)

February 26, 2027

Study Registration Dates

First Submitted

June 8, 2021

First Submitted That Met QC Criteria

June 8, 2021

First Posted (Actual)

June 11, 2021

Study Record Updates

Last Update Posted (Actual)

April 11, 2024

Last Update Submitted That Met QC Criteria

April 10, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6482-015
  • MK-6482-015 (Other Identifier: Merck)
  • PT2977 (Other Identifier: Former name)
  • jRCT2011220024 (Registry Identifier: Japan Registry of Clinical Trials (jRCT))
  • 2020-005028-13 (EudraCT Number)
  • 2023-504853-11-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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