Researchers found improved progression-free survival (PFS) with pimitespib compared with placebo in patients with previously treated advanced gastrointestinal stromal tumors (GISTs). The study, published in the Annals of Oncology, also found an acceptable safety profile and a benefit to pimitespib regardless of KIT mutations.

“Here, we report the results from the placebo-controlled, phase 3 study evaluating the efficacy and safety of pimitespib as fourth-line therapy in patients with advanced GIST refractory to imatinib, sunitinib, and regorafenib,” the authors wrote. “Pimitespib could be considered as a new treatment option in the fourth-line setting for GIST refractory to standard therapies.”

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The research team conducted a randomized, double-blind, placebo-controlled, multicenter phase 3 trial including 2 treatment periods, 1 with pimitespib vs placebo, and the second optional period for patients with the progressive disease to take pimitespib open-label treatment. A total of 86 patients were randomized to placebo or pimitespib. The primary outcome of the trial, significantly improved PFS, was achieved with pimitespib compared with placebo.

The authors note that their results are significant for the treatment of GIST because the mechanism of action of pimitespib is different from standard tyrosine kinase inhibitors such as ripretinib, which are used in earlier lines of treatment. The safety profile of pimitespib was found to be favorable and in line with the results of the authors’ phase 2 study.

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The most common adverse event was diarrhea, but the incidence of treatment discontinuation due to adverse events was low (5.2%) and manageable with dose adjustments. Therefore the authors suggest pimitespib could represent a fourth-line treatment for patients with GISTs who do not respond to other treatments.


Kurokawa Y, Honma Y, Sawaki A. Pimitespib in patients with advanced gastrointestinal stromal tumor (CHAPTER-GIST-301): a randomized, double-blind, placebo-controlled phase 3 trial. Ann Oncol. Published online June 7, 2022. doi:10.1016/j.annonc.2022.05.518