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NCT Number: NCT04924075

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)

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).

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Key information

Conditions

Pheochromocytoma/Paraganglioma Abnormalities, Multiple Adenoma Adenoma, Islet Cell Advanced Gastrointestinal Stromal Tumor Angiomatosis Cardiovascular Diseases Ciliopathies Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Genetic Diseases, Inborn HIF-2α Mutated Cancers Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Nervous System Diseases Neurocutaneous Syndromes Neuroectodermal Tumors Neuroendocrine Tumors Pancreatic Diseases Pancreatic Neoplasms Pancreatic Neuroendocrine Tumor Paraganglioma Pheochromocytoma Vascular Diseases Von Hippel-Lindau Disease

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

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

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Belzutifan

Drug

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

Other names: MK-6482, WELIREG™

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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).

  4. 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.

  5. 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.

  6. Number of Participants Who Experience an Adverse Event (AE)

    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.

  7. Number of Participants Who Discontinue Study Treatment 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.

  8. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Toll Free Number

CONTACT

[email protected]

1-888-577-8839

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2029
Study completion
2029
First posted
Jun 11, 2021
Registry last updated
Jul 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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