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
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).
Arms & interventions
- DrugBelzutifan
Belzutifan, 120 mg, oral, once daily (QD) until progressive disease or discontinuation.
Outcome measures
Primary
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.
Time frame: Up to approximately 5.5 years
Secondary
Duration of Response (DOR) as Assessed by BICR
Time frame: Up to approximately 5.5 years
Time to Response (TTR) as Assessed by BICR
Time frame: Up to approximately 5.5 years
Disease Control Rate (DCR) as Assessed by BICR
Time frame: Up to approximately 5.5 years
Progressive Free Survival (PFS) as Assessed by BICR
Time frame: Up to approximately 5.5 years
Overall Survival (OS)
Time frame: Up to approximately 5.5 years
Number of Participants Who Experience an Adverse Event (AE)
Time frame: Up to approximately 5.5 years
Number of Participants Who Discontinue Study Treatment Due to an AE
Time frame: Up to approximately 5.5 years
Time to Surgery (TTS)
Time frame: Up to approximately 5.5 years
Eligibility criteria
Study locations (14)
Cedars-Sinai Medical Center ( Site 0110)
Los Angeles, California, 90048
Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0130)
Chicago, Illinois, 60611
Northwestern Medicine Cancer Center - Warrenville ( Site 0134)
Warrenville, Illinois, 60555
University of Iowa ( Site 0104)
Iowa City, Iowa, 52242
Johns Hopkins Hospital-Sidney Kimmel Comprehensive Cancer Center - Developmental Therapeutics ( Site 0108)
Baltimore, Maryland, 21287
National Institutes of Health ( Site 0125)
Bethesda, Maryland, 20892
Massachusetts General Hospital ( Site 0111)
Boston, Massachusetts, 02114
University of Michigan ( Site 0126)
Ann Arbor, Michigan, 48109
Washington University-Internal Medicine/Oncology ( Site 0124)
St Louis, Missouri, 63110
Icahn School of Medicine at Mount Sinai ( Site 0123)
New York, New York, 10029
Penn Medicine: University of Pennsylvania Health System-Heme/Onc ( Site 0127)
Philadelphia, Pennsylvania, 19104
SCRI Oncology Partners ( Site 7000)
Nashville, Tennessee, 37203
Vanderbilt University Medical Center ( Site 0107)
Nashville, Tennessee, 37232
University of Texas MD Anderson Cancer Center ( Site 0112)
Houston, Texas, 77030
References
- Jimenez C, Andreassen M, Durand A, Moog S, Hendifar A, Welin S, Spada F, Sharma R, Wolin E, Ruether J, Garcia-Carbonero R, Fassnacht M, Capdevila J, Del Rivero J, Iliopoulos O, Huillard O, Jang R, Mai K, Artamonova E, Hallqvist A, Else T, Odeleye-Ajakaye A, Gozman A, Naik GS, Berruti A; LITESPARK-015 Investigators. Belzutifan for Advanced Pheochromocytoma or Paraganglioma. N Engl J Med. 2025 Nov 20;393(20):2012-2022. doi: 10.1056/NEJMoa2504964. Epub 2025 Oct 18.(PubMed)