Recruiting
Phase 2

Belzutifan

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT04924075

Conditions

Pheochromocytoma/Paraganglioma

Pancreatic Neuroendocrine Tumor

Von Hippel-Lindau Disease

Advanced Gastrointestinal Stromal Tumor

HIF-2α Mutated Cancers

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

Interventions

Belzutifan

Study Details

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

Pheochromocytoma/Paraganglioma

Pancreatic Neuroendocrine Tumor

Von Hippel-Lindau Disease

Advanced Gastrointestinal Stromal Tumor

HIF-2α Mutated Cancers

Study ID

NCT04924075

Start date

Aug 12, 2021

Status verified date

Sep, 2026

Completion date

Dec 27, 2029

Anticipated

Primary completion date

Dec 27, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

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

355 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Belzutifan

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

Interventions

Belzutifan

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

Primary outcome measure

  • Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 5.5 years ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839Trialsites@msd.com

Locations

Cedars-Sinai Medical Center ( Site 0110)

Recruiting

Los Angeles, California, United States, 90048

Contacts

Study Coordinator

310-967-2781

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

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Study Coordinator

312-695-1310

Northwestern Medicine Cancer Center - Warrenville ( Site 0134)

Recruiting

Warrenville, Illinois, United States, 60555

Contacts

Study Coordinator

312-695-1310

University of Iowa ( Site 0104)

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Study Coordinator

319-356-2148

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

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Study Coordinator

410-502-5140

National Institutes of Health ( Site 0125)

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

Study Coordinator

240-858-3851

Massachusetts General Hospital ( Site 0111)

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Study Coordinator

617-724-4000

University of Michigan ( Site 0126)

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Study Coordinator

734-647-8902

SCRI Oncology Partners ( Site 7000)

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

Study Coordinator

615-329-7274

Vanderbilt University Medical Center ( Site 0107)

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Study Coordinator

800-811-8480

University of Texas MD Anderson Cancer Center ( Site 0112)

Recruiting

Houston, Texas, United States, 77030

Contacts

Study Coordinator

713-792-2841

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

Recruiting

Calgary, Alberta, Canada, T2N 5G2

Contacts

Study Coordinator

403-521-3165

Princess Margaret Cancer Centre ( Site 0202)

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contacts

Study Coordinator

416-946-4501 x6508

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 3, 2026

Last verified

Sep, 2026

Keywords

  • HIF-2α
  • Pheochromocytoma/paraganglioma
  • Pancreatic NET

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-03.