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Open Access 01-08-2019 | Prostate Cancer | Original Article

Phase I study of ipatasertib as a single agent and in combination with abiraterone plus prednisolone in Japanese patients with advanced solid tumors

Authors: Toshihiko Doi, Yutaka Fujiwara, Nobuaki Matsubara, Junichi Tomomatsu, Satoru Iwasa, Akari Tanaka, Chihiro Endo-Tsukude, Shintaro Nakagawa, Shunji Takahashi

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2019

Abstract

Purpose

Ipatasertib is a selective inhibitor of Akt, a frequently activated protein kinase in human cancers. The current study assessed the safety, tolerability, and pharmacokinetics of ipatasertib in Japanese patients with solid tumors.

Methods

This was a phase I, open-label, 3 + 3 dose-escalation study conducted in two stages. In stage I, Japanese patients with solid tumors were administered ipatasertib 200, 400, or 600 mg/day for 21 days of a 28-day cycle. In stage II, Japanese patients with castration-resistant prostate cancer were administered ipatasertib 200 or 400 mg/day in combination with abiraterone and prednisolone in 28-day cycles. Dose-limiting toxicity (DLT) was assessed at each dose before enrolling patients at a higher dose; DLT was used to determine the maximum tolerated dose (MTD) and maximum administered dose (MAD). Pharmacokinetic parameters were assessed after a single dose and at steady state.

Results

Fifteen patients were enrolled in Stage I and six in Stage II. The ipatasertib MTD was 600 mg as monotherapy and MAD was 400 mg in combination with abiraterone and prednisolone. Ipatasertib plasma exposure was dose proportional across the dose range, and was not markedly affected by concurrent administration of abiraterone plus prednisolone. Stable disease (SD) was observed in eight patients treated with ipatasertib monotherapy (53.3%); four patients had SD and one had complete response with ipatasertib plus abiraterone and prednisolone.

Conclusions

Ipatasertib, at the monotherapy MTD of 600 mg/day and MAD of 400 mg/day in combination with abiraterone and prednisolone, was safe and tolerable in Japanese patients with solid tumors.

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Title: Phase I study of ipatasertib as a single agent and in combination with abiraterone plus prednisolone in Japanese patients with advanced solid tumors
Authors: Toshihiko Doi
Yutaka Fujiwara
Nobuaki Matsubara
Junichi Tomomatsu
Satoru Iwasa
Akari Tanaka
Chihiro Endo-Tsukude
Shintaro Nakagawa
Shunji Takahashi
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keywords: Prostate Cancer
Solid Tumor
Pharmacokinetics
Prostate Cancer
Prednisolone
Published in: Cancer Chemotherapy and Pharmacology / Issue 2/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03882-7

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