• Toshihiko Doi, Nozomu Fuse, Takayuki Yoshino, Takashi Kojima, Hideaki Bando, Hideaki Miyamoto, Masato Kaneko, Motonobu Osada, and Atsushi Ohtsu.
• National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa-shi, Chiba, 277-8577, Japan. tdoi@east.ncc.go.jp.
• Cancer Chemother. Pharmacol. 2017 Jan 1; 79 (1): 89-98.

PurposeTo evaluate the safety, tolerability, pharmacokinetics, and efficacy of the intravenously administered pan-PI3K inhibitor copanlisib in Japanese patients with advanced or refractory solid tumors.MethodsA Phase I open-label study in Japanese patients with advanced or refractory solid tumors was carried out. Patients received a single intravenous dose of either copanlisib 0.4 mg/kg or copanlisib 0.8 mg/kg, dosed intermittently on days 1, 8, and 15 of a 28-day cycle. Safety was monitored throughout the study. Plasma copanlisib levels were measured for pharmacokinetic analysis.ResultsTen patients were enrolled and treated; three received copanlisib 0.4 mg/kg and seven received copanlisib 0.8 mg/kg. Overall, median duration of treatment was 6.2 weeks. No patients treated at 0.4 mg/kg experienced a dose-limiting toxicity, and the maximum tolerated dose in Japanese patients was determined to be 0.8 mg/kg. Adverse events were recorded in all ten patients; the most common were hyperglycemia, hypertension, and constipation. Copanlisib pharmacokinetic exposures displayed near dose-proportionality, with no accumulation. No patients achieved a complete or partial response, and disease control rate was 40.0%.ConclusionsCopanlisib was well tolerated in Japanese patients with advanced or refractory solid tumors, and the maximum tolerated dose was determined to be 0.8 mg/kg. Copanlisib demonstrated near dose-proportional pharmacokinetics and preliminary disease control, warranting further investigation.Clinical Trial Registration NumberNCT01404390.

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