Phase I Study of the Focal Adhesion Kinase Inhibitor BI853520 in Japanese and Taiwanese Patients with Advanced or Metastatic Solid Tumors

BackgroundFocal 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 BI853520 in a predominantly Caucasian population with advanced or metastatic non-hematologic malignancies demonstrated acceptable tolerability and favorable pharmacokinetics.ObjectiveThis study was undertaken to investigate the safety, tolerability, and maximum tolerated dose (MTD) of BI853520 in Japanese and Taiwanese patients with advanced solid tumors.Patients and MethodsIn this open-label, phaseI, dose-finding study, BI853520 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 65years) were treated at two sites in Japan and Taiwan.ResultsThe median duration of treatment was 1.2months (range 0.2-7.7). As no dose-limiting toxicities were observed during cycle 1 in the 50, 100, or 200mg cohorts, the MTD of BI853520 was determined to be 200mg QD. Drug-related adverse events were reported in 19 patients (90%), and all except one were of grade1 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 3.7months.ConclusionsThis trial demonstrated a manageable and acceptable safety profile, favorable pharmacokinetics, and potential anti-tumor activity of BI853520 in pretreated Japanese and Taiwanese patients with advanced or metastatic solid tumors.Clinical trials registrationNCT01905111.