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)

Study Overview

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).

N/A

Pheochromocytoma/Paraganglioma
Pancreatic Neuroendocrine Tumor
Von Hippel-Lindau Disease
Advanced Gastrointestinal Stromal Tumor
HIF-2α Mutated Cancers

DRUG: Belzutifan

6482-015
MK-6482-015 (OTHER Identifier) (OTHER: MSD)
PT2977 (OTHER Identifier) (OTHER: Former name)
jRCT2011220024 (REGISTRY Identifier) (REGISTRY: Japan Registry of Clinical Trials (jRCT))
2023-504853-11-00 (REGISTRY Identifier) (REGISTRY: EU CT)
2020-005028-13 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-06-08	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-08-12
First Submitted that Met QC Criteria 2021-06-08	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-08-14
First Posted (ACTUAL) 2021-06-11	Results First Posted N/A	Last Verified 2025-08

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

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.

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.

Primary Outcome Measures	Measure Description	Time Frame
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.	Up to approximately 5.5 years

Secondary Outcome Measures	Measure Description	Time Frame
Duration of Response (DOR) as Assessed by BICR	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	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	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	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)	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)	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	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)	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

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

Name: Toll Free Number

Phone Number: 1-888-577-8839

Email: Trialsites@msd.com

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
12 Years

Accepts Healthy Volunteers:

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 BI: 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

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

Collaborators and Investigators

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

Investigators

STUDY_DIRECTOR: Medical Director, Merck Sharp & Dohme LLC

Publications

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

General Publications

No publications available

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