Pimitespib in patients with advanced gastrointestinal stromal tumors in Japan: an expanded access program

Abstract Background Pimitespib, an oral heat shock protein 90 inhibitor, significantly prolonged progression-free survival in patients with advanced gastrointestinal stromal tumors (GIST) in CHAPTER-GIST-301 study. This expanded access program was conducted to evaluate the safety and efficacy of pimitespib in Japanese patients with advanced GIST.Methods This multicenter, open-label, single-arm study was conducted in patients (≥ 20 years) with histologically confirmed GIST who had been previously treated with imatinib, sunitinib and regorafenib and had an Eastern Cooperative Oncology Group performance status of 0–1. Patients received pimitespib 160 mg/day for five days, followed by a 2-day rest, in 21-day cycles.Results Between February and August 2022, 23 patients were enrolled (median age 59.0 years). Over a median pimitespib treatment duration of 81.0 days, adverse events occurred in 22 patients (95.7%). The most common adverse events were diarrhea (73.9%), nausea (39.1%) and increased blood creatinine (30.4%). Serious adverse events occurred in two patients (tumor hemorrhage and tumor pain); neither was related to pimitespib. One patient had grade 3 diarrhea that was considered treatment-related. Four patients (17.4%) had eye disorders, all of which were grade 1 and treatment-related. The median progression-free survival was 4.2 months (95% confidence interval [CI] 1.9–6.2), the overall response rate was 0% (95% CI 0–16.1) and the disease control rate was 66.7% (95% CI 43.0–85.4).Conclusions Pimitespib was well tolerated and effective in patients with advanced GIST in real-world practice in Japan. No new safety signals were identified.Trial registration jRCT2031210526 registered 1 February 2022.