Phase I Study of the Focal Adhesion Kinase Inhibitor BI 853520 in Japanese and Taiwanese Patients with Advanced or Metastatic Solid Tumors
Journal
Targeted Oncology
Journal Volume
14
Journal Issue
1
Pages
57-65
Date Issued
2019
Author(s)
Doi T.
Shitara K.
Naito Y.
Sarashina A.
Pronk L.C.
Takeuchi Y.
Abstract
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. ? 2019, The Author(s).
SDGs
Other Subjects
aspartate aminotransferase; bi 853520; bilirubin; creatinine; focal adhesion kinase inhibitor; unclassified drug; focal adhesion kinase 1; protein kinase inhibitor; PTK2 protein, human; abdominal pain; advanced cancer; aged; anemia; antineoplastic activity; area under the curve; Article; backache; cohort analysis; decreased appetite; dehydration; diarrhea; disease control; disease severity; dose response; drug accumulation; drug dose comparison; drug dose escalation; drug efficacy; drug half life; drug safety; drug tolerability; Dupuytren contracture; erectile dysfunction; fatigue; female; human; inguinal hernia; Japan; Japanese (people); maculopapular rash; major clinical study; male; maximum concentration; maximum tolerated dose; metastasis; multiple cycle treatment; nausea; open study; phase 1 clinical trial; priority journal; proteinuria; side effect; Taiwan; Taiwanese; treatment duration; vomiting; adult; clinical trial; follow up; metastasis; middle aged; neoplasm; pathology; prognosis; tissue distribution; Adult; Aged; Female; Focal Adhesion Kinase 1; Follow-Up Studies; Humans; Japan; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neoplasms; Prognosis; Protein Kinase Inhibitors; Taiwan; Tissue Distribution
Publisher
Springer-Verlag France
Type
journal article