Phase I study of taselisib in Japanese patients with advanced solid tumors or hormone receptor-positive advanced breast cancer

Summary

Taselisib is a potent and selective phosphatidylinositide 3-kinase (PI3K) inhibitor. This paper reports the first study of taselisib administration in Japanese patients. The aim of this two-stage, phase I, multicenter, open-label, dose-escalation study was to evaluate the safety, pharmacokinetics, and preliminary efficacy of taselisib as monotherapy in Japanese patients with advanced solid tumors (Stage 1), and as part of combination therapy in Japanese patients with hormone receptor (HR)-positive locally advanced or recurrent breast cancer (Stage 2). In Stage 1, oral taselisib tablets 2, 4, and 6 mg/day were administered in 28-day cycles. In Stage 2, successive cohorts of patients received oral taselisib tablets (2 or 4 mg/day) with intramuscular fulvestrant 500 mg. Nine and six patients were enrolled in Stage 1 and Stage 2, respectively. Taselisib was well tolerated. No dose-limiting toxicities were experienced in any cohort of patients and no deaths were observed. The most common treatment-related adverse events in Stage 1 and Stage 2 were rash (55.6%, 66.7%), diarrhea (44.4%, 66.7%), stomatitis (44.4%, 66.7%). Taselisib was rapidly absorbed after administration; its half-life was 12.9–32.0 hours in Stage 1 and 16.1–26.5 hours in Stage 2. Two patients achieved partial response (PR) and five patients had stable disease (SD) in Stage 1, and one patient had PR and five patients had SD in Stage 2. All patients with PR were positive for PIK3CA gene mutations. These preliminary data suggest that taselisib may be effective in patients with PIK3CA-mutated solid tumors or HR-positive advanced breast cancer.

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