Advanced Gastrointestinal Stromal Tumor, HIF-2α Mutated Cancers, Pancreatic Neuroendocrine Tumor, Pheochromocytoma/Paraganglioma, Von Hippel-Lindau Disease
Conditions
Keywords
HIF-2α, Pheochromocytoma/paraganglioma, Pancreatic NET
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).
Interventions
DRUGBelzutifan
Belzutifan, 120 mg, oral, once daily (QD) until progressive disease or discontinuation.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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. |
| Overall Survival (OS) | Up to approximately 5.5 years | OS is the time from first dose of belzutifan until death from any cause. |
| Number of Participants Who Experience an Adverse Event (AE) | 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. |
| Number of Participants Who Discontinue Study Treatment 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. |
| 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. |
Countries
Australia, Canada, Chile, China, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, Norway, Portugal, Russia, Singapore, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed