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

作者：Doi Toshihiko^*; Fuse Nozomu; Yoshino Takayuki; Kojima Takashi; Bando Hideaki; Miyamoto Hideaki; Kaneko Masato; Osada Motonobu; Ohtsu Atsushi

来源：Cancer Chemotherapy and Pharmacology, 2017, 79(1): 89-98.

DOI：10.1007/s00280-016-3198-0

• Copanlisib
• PI3K inhibitor
• Japanese
• Solid tumors

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.
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.
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%.
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.
NCT01404390.

• 出版日期2017-1