A Phase I Study of the Pharmacokinetics and Safety of Ipatasertib, an Akt Inhibitor in Chinese Patients With Locally Advanced or Metastatic Solid Tumors

Abstract

Purpose

Ipatasertib is a selective inhibitor of Akt, a frequently activated protein kinase that plays a critical role in human cancers. The current clinical trial aimed to assess the pharmacokinetic properties, safety, and tolerability of ipatasertib administered to Chinese patients with locally advanced or metastatic solid tumors.

Methods

A Phase I, single-arm, open-label study was performed in Chinese patients with locally advanced or metastatic solid tumors for whom standard therapy either does not exist or has proven ineffective. Four hundred milligrams of ipatasertib was administered to patients as a single agent, starting with a single dose for 7 days and continuous daily dosing for 21 days, followed by 7 days off schedule. The pharmacokinetic properties of ipatasertib and its major metabolite M1 (GO37220) after single and multiple dose administration were assessed using a validated liquid chromatography–tandem mass spectrometry assay method. Safety was assessed throughout the study, and adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Tumor response was assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1.

Findings

Fourteen patients were enrolled, and all enrolled patients received at least 1 dose of the study treatment. Ipatasertib and M1 exposures were slightly higher than previously reported but comparable with exposures observed within the Asian population. Ipatasertib as a single agent demonstrated a manageable safety profile in Chinese patients, which is aligned with prior observation in global studies. Limited efficacy was observed in these patients with heavily pretreated diverse solid tumors.

Implications

This study of the pharmacokinetic properties, safety, and efficacy of ipatasertib in Chinese patients eventually contributed toward the development of Akt inhibitors in China. ClinicalTrials.gov identifier: NCT04341259.