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

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.

• Authors: Toshihiko Doi, Nozomu Fuse, Takayuki Yoshino, Takashi Kojima, Hideaki Bando, Hideaki Miyamoto, Masato Kaneko, Motonobu Osada, Atsushi Ohtsu
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 79 Issue 1 Pg. 89-98 (Jan 2017) ISSN: 1432-0843 [Electronic] Germany
• PMID: 27915408 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Antineoplastic Agents
• Phosphoinositide-3 Kinase Inhibitors
• Pyrimidines
• Quinazolines
• copanlisib

Topics

• Aged
• Antineoplastic Agents (therapeutic use)
• Female
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (drug therapy)
• Phosphoinositide-3 Kinase Inhibitors
• Pyrimidines (adverse effects, pharmacokinetics, therapeutic use)
• Quinazolines (adverse effects, pharmacokinetics, therapeutic use)