Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 2

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

NCT ID: NCT04924075Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-08

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).

Arms & interventions

  • DrugBelzutifan

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

Outcome measures

Primary

  • 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.

    Time frame: Up to approximately 5.5 years

Secondary

  • Duration of Response (DOR) as Assessed by BICR

    Time frame: Up to approximately 5.5 years

  • Time to Response (TTR) as Assessed by BICR

    Time frame: Up to approximately 5.5 years

  • Disease Control Rate (DCR) as Assessed by BICR

    Time frame: Up to approximately 5.5 years

  • Progressive Free Survival (PFS) as Assessed by BICR

    Time frame: Up to approximately 5.5 years

  • Overall Survival (OS)

    Time frame: Up to approximately 5.5 years

  • Number of Participants Who Experience an Adverse Event (AE)

    Time frame: Up to approximately 5.5 years

  • Number of Participants Who Discontinue Study Treatment Due to an AE

    Time frame: Up to approximately 5.5 years

  • Time to Surgery (TTS)

    Time frame: Up to approximately 5.5 years

Eligibility criteria

Sex: AllAge: 12 Years and olderHealthy volunteers: No
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 locations (14)

Cedars-Sinai Medical Center ( Site 0110)

Los Angeles, California, 90048

Recruiting
Study Coordinator · Contact

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

Chicago, Illinois, 60611

Recruiting
Study Coordinator · Contact

Northwestern Medicine Cancer Center - Warrenville ( Site 0134)

Warrenville, Illinois, 60555

Recruiting
Study Coordinator · Contact

University of Iowa ( Site 0104)

Iowa City, Iowa, 52242

Recruiting
Study Coordinator · Contact

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

Baltimore, Maryland, 21287

Recruiting
Study Coordinator · Contact

National Institutes of Health ( Site 0125)

Bethesda, Maryland, 20892

Recruiting
Study Coordinator · Contact

Massachusetts General Hospital ( Site 0111)

Boston, Massachusetts, 02114

Recruiting
Study Coordinator · Contact

University of Michigan ( Site 0126)

Ann Arbor, Michigan, 48109

Recruiting
Study Coordinator · Contact

Washington University-Internal Medicine/Oncology ( Site 0124)

St Louis, Missouri, 63110

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

SCRI Oncology Partners ( Site 7000)

Nashville, Tennessee, 37203

Recruiting
Study Coordinator · Contact

Vanderbilt University Medical Center ( Site 0107)

Nashville, Tennessee, 37232

Recruiting
Study Coordinator · Contact

University of Texas MD Anderson Cancer Center ( Site 0112)

Houston, Texas, 77030

Recruiting
Study Coordinator · Contact

References

  • 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)