title: A Phase I study of intravenous PI3K inhibitor copanlisib in Japanese patients with advanced or refractory solid tumors.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  NCT01404390.
authors.affiliation: National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa-shi, Chiba, 277-8577, Japan. tdoi@east.ncc.go.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Doi
authors.affiliation: National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa-shi, Chiba, 277-8577, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fuse
authors.affiliation: National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa-shi, Chiba, 277-8577, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa-shi, Chiba, 277-8577, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.affiliation: National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa-shi, Chiba, 277-8577, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bando
authors.affiliation: Department of Gastroenterology and Hepatology, Kumamoto University, 2-39-1 Kurokami, Chuo Ward, Kumamoto, 860-8555, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyamoto
authors.affiliation: Bayer Yakuhin, Ltd., 2-4-9, Umeda, Kita-ku, Osaka, 530-0001, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Bayer Yakuhin, Ltd., 2-4-9, Umeda, Kita-ku, Osaka, 530-0001, Japan.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Osada
authors.affiliation: National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa-shi, Chiba, 277-8577, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011743:Pyrimidines; D011799:Quinazolines; C000589253:copanlisib
keywords: Copanlisib; Japanese; PI3K inhibitor; Solid tumors