Phase I Study of the Focal Adhesion Kinase Inhibitor BI 853520 in Japanese and Taiwanese Patients with Advanced or Metastatic Solid Tumors

Autor: Kohei Shitara, Ann-Lii Cheng, Yoshito Takeuchi, James Chih-Hsin Yang, Akiko Sarashina, Linda C Pronk, Yoichi Naito, Chia-Chi Lin, Toshihiko Doi
Rok vydání: 2019
Předmět:
Zdroj: Targeted Oncology
ISSN: 1776-260X
1776-2596
Popis: Background Focal adhesion kinase (FAK) inhibitors have demonstrated anti-tumor activity preclinically and are currently being evaluated in humans. A first-in-human study evaluating the novel FAK inhibitor BI 853520 in a predominantly Caucasian population with advanced or metastatic non-hematologic malignancies demonstrated acceptable tolerability and favorable pharmacokinetics. Objective This study was undertaken to investigate the safety, tolerability, and maximum tolerated dose (MTD) of BI 853520 in Japanese and Taiwanese patients with advanced solid tumors. Patients and Methods In this open-label, phase I, dose-finding study, BI 853520 was administered once daily (QD) in a continuous daily dosing regimen with 28-day cycles and escalating doses to sequential cohorts of patients. Twenty-one patients (62% male; median age 65 years) were treated at two sites in Japan and Taiwan. Results The median duration of treatment was 1.2 months (range 0.2–7.7). As no dose-limiting toxicities were observed during cycle 1 in the 50, 100, or 200 mg cohorts, the MTD of BI 853520 was determined to be 200 mg QD. Drug-related adverse events were reported in 19 patients (90%), and all except one were of grade 1 or 2. Pharmacokinetic parameters were supportive of a once-daily dosing schedule. A confirmed objective response rate of 5% and disease control rate of 29% were achieved; median duration of disease control was 3.7 months. Conclusions This trial demonstrated a manageable and acceptable safety profile, favorable pharmacokinetics, and potential anti-tumor activity of BI 853520 in pretreated Japanese and Taiwanese patients with advanced or metastatic solid tumors. Clinical trials registration NCT01905111. Electronic supplementary material The online version of this article (10.1007/s11523-019-00620-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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