PEMIGIST: Phase II Study of Pemigatinib in SDH-deficient GIST

Summary

Gastrointestinal stromal tumors (GISTs) are a group of rare cancers, with an incidence of 4,000 to 6,000 new cases per year in the United States. Approximately 10-15% of adult GISTs and the majority of pediatric GISTs are driven by the loss of the SDH protein complex. While surgery is the standard of care for localized disease, the majority of patients with advanced and metastatic disease do not respond to most standard of care treatments. Thus, new treatment options for these patients are needed.

Preclinical studies have demonstrated that the use of FGFR inhibitors in SDH-deficient GIST PDX models resulted in significant tumor regression. It was reproducible across three different FGFR inhibitors and appears to be a class effect. As a result, the researchers conducted and completed a phase II study of rogaratinib, a FGFR inhibitor, in locally advanced and metastatic SDH-deficient GIST. Rogaratinib demonstrated an objective response rate of 41% and the median progression-free survival (the length of time after starting treatment until the cancer grows or spreads) had not been reached. Unfortunately, rogaratinib is no longer being developed by any pharmaceutical company and became unavailable as of June 2025. This is a challenging situation for patients with SDH-deficient GIST, as this is a promising treatment based on the high and durable response rate in this population. Due to the class effect seen in the preclinical studies, the investigators propose a study with pemigatinib, an oral FGFR inhibitor already approved by the FDA in other cancer types. This phase II study will assess the response rate of pemigatinib in patients with locally advanced or metastatic SDH-deficient GIST. If successful, this trial could change the standard of care for patients with advanced SDH-deficient GIST and allow the investigators to petition the National Comprehensive Cancer Network (NCCN) for updated treatment guidelines.

Clinicaltrials.gov Identifier: NCT07434843