A Phase I study of intravenous PI3K inhibitor copanlisib in Japanese patients with advanced or refractory solid tumors

Toshihiko Doi, Nozomu Fuse, Takayuki Yoshino, Takashi Kojima, Hideaki Bando, Hideaki Miyamoto, Masato Kaneko, Motonobu Osada, Atsushi Ohtsu, Toshihiko Doi, Nozomu Fuse, Takayuki Yoshino, Takashi Kojima, Hideaki Bando, Hideaki Miyamoto, Masato Kaneko, Motonobu Osada, Atsushi Ohtsu

Abstract

Purpose: To evaluate the safety, tolerability, pharmacokinetics, and efficacy of the intravenously administered pan-PI3K inhibitor copanlisib in Japanese patients with advanced or refractory solid tumors.

Methods: A 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.

Results: Ten 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%.

Conclusions: Copanlisib 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 number: NCT01404390.

Keywords: Copanlisib; Japanese; PI3K inhibitor; Solid tumors.

Conflict of interest statement

Toshihiko Doi, Nozomu Fuse, Takashi Kojima, Hideaki Bando, Hideaki Miyamoto, and Atsushi Ohtsu have no relevant financial disclosures to declare. Takayuki Yoshino has received research funding from Sumitomo Dainippon Pharma. Masato Kaneko and Motonobu Osada are employees of Bayer Yakuhin, Ltd. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Geometric mean (geometric standard deviation) of copanlisib concentrations in plasma on cycle 1, day 1. Error bars represent geometric standard deviation

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