Aim: We evaluated the efficacy and safety of TAS-116, a novel class of an orally active selective inhibitor of heat shock protein 90, in patients with advanced gastrointestinal stromal tumour (GIST) after failure of three or more lines of standard treatment with imatinib, sunitinib and regorafenib. Methods: In this single-arm phase II study, patients received 160 mg/day oral TAS-116 for five consecutive days, followed by a 2-day rest. The primary end-point was centrally assessed progression-free survival (PFS). The secondary end-points were objective response rate, disease control rate, overall survival (OS), metabolic response rate, safety, pharmacokinetics and pharmacogenomics. Results: Forty-one patients were enrolled in Japan, and 40 patients underwent efficacy and safety evaluation. At the cut-off date, the median PFS was 4.4 months (95% confidence interval [CI], 2.8–6.0) and 12-week progression-free rate was 73.4% (95% CI, 58.1–88.7). Thirty-four patients (85.0%) had stable disease for ≥ 6 weeks. The median OS was 11.5 months (95% CI, 7.0–not reached). All patients experienced at least one treatment-related adverse event (AE), including diarrhoea (80.0%), decreased appetite (45.0%) and increase in blood creatinine level (42.5%). Grade ≥3 AEs and treatment-related grade ≥3 AEs occurred in 23 (57.5%) and 21 (52.5%) patients, respectively. All AEs resolved after dose modification, and no TAS-116–related AEs led to treatment discontinuation. Conclusion: TAS-116 showed significant activity in advanced GIST refractory to standard treatment. Further development of TAS-116 is warranted. Trial registration: JapicCTI-163182.
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