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)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Belzutifan

Study type: Interventional

Funder types: Industry

Identifiers

NCT04924075

6482-015

2023-504853-11 (Registry Identifier)

jRCT2011220024 (Registry Identifier)

MK-6482-015 (Other Identifier)

PT2977 (Other Identifier)

2020-005028-13 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 322 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 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

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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322 participants in 1 patient group

Belzutifan

Experimental group

Description:

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

Treatment:

Drug: Belzutifan