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)

Phase 2

Recruiting

• Conditions: Pheochromocytoma/Paraganglioma; HIF-2α Mutated Cancers; Pancreatic Neuroendocrine Tumor; Von Hippel-Lindau Disease; Advanced Gastrointestinal Stromal Tumor
• Interventions: Drug: Belzutifan

• Registration Number: NCT04924075
• Lead Sponsor: Merck Sharp & Dohme LLC

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-08
• Study First Submitted QC: 2021-06-08
• Study First Posted: 2021-06-11
• Study Start: 2021-08-12
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-16
• Last Update Posted: 2025-07-17
• Primary Completion: 2029-06-04
• Study Completion: 2029-06-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 322

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)	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 Outcome Measures

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

Trial Locations

Locations (77)

Cedars-Sinai Medical Center ( Site 0110); 🇺🇸 Los Angeles, California, United States

Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0130); 🇺🇸 Chicago, Illinois, United States

University of Iowa ( Site 0104); 🇺🇸 Iowa City, Iowa, United States

Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - Developmental Therapeutics ( Site 0108); 🇺🇸 Baltimore, Maryland, United States

National Institutes of Health ( Site 0125); 🇺🇸 Bethesda, Maryland, United States

Massachusetts General Hospital ( Site 0111); 🇺🇸 Boston, Massachusetts, United States

University of Michigan ( Site 0126); 🇺🇸 Ann Arbor, Michigan, United States

Washington University-Internal Medicine/Oncology ( Site 0124); 🇺🇸 Saint Louis, Missouri, United States

Icahn School of Medicine at Mount Sinai ( Site 0123); 🇺🇸 New York, New York, United States

Penn Medicine: University of Pennsylvania Health System-Heme/Onc ( Site 0127); 🇺🇸 Philadelphia, Pennsylvania, United States

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