Dataset Information

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

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.

SUBMITTER: Doi T

PROVIDER: S-EPMC6407737 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Doi Toshihiko T Yang James Chih-Hsin JC Shitara Kohei K Naito Yoichi Y Cheng Ann-Lii AL Sarashina Akiko A Pronk Linda C LC Takeuchi Yoshito Y Lin Chia-Chi CC

Targeted oncology 20190201 1

<h4>Background</h4>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.<h4>Objective</h4>This study was undertaken to investigate the safety, tolerability, and maximum tolerated dose ...[more]

PMID: 30725402

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Project description:BACKGROUND:BI 853520 is a potent inhibitor of focal adhesion kinase and is currently under clinical development for the treatment of non-hematological malignancies. OBJECTIVE:The objective of this study was to evaluate the effect of food and liquid dispersion on the pharmacokinetics of BI 853520 in two open-label, crossover substudies. PATIENTS AND METHODS:Sixteen patients with advanced solid tumors were enrolled in each substudy. The order of administration was randomized, and pharmacokinetic samples were collected for 48 h after administration of a 200 mg dose of BI 853520. Lack of effect would be demonstrated if the 90% confidence interval (CI) of the ratio of the adjusted geometric mean (GMR) of the area under the plasma curve (area under the plasma concentration-time curve from time zero to the last quantifiable concentration at tz [[Formula: see text]] and observed area under the plasma concentration-time curve extrapolated from time zero to infinity [AUC0-∞,obs]) and maximum plasma concentration (Cmax) did not cross the 80-125% (bioequivalence) boundaries. RESULTS:Adjusted GMRs (90% CIs) for the fed versus fasted state were 92.46% (74.24-115.16), 98.17% (78.53-122.74), and 87.34% (71.04-107.38) for [Formula: see text], AUC0-∞,obs, and Cmax, respectively. Although the 90% CIs were not within bioequivalence limits for the food-effect study, the limited reductions in these pharmacokinetic parameters after administration with a high-fat meal are unlikely to be clinically relevant. Compared with a tablet, administration of BI 853520 as a liquid dispersion did not strongly affect [Formula: see text], AUC0-∞,obs, or Cmax, resulting in adjusted GMRs (90% CIs) of 1.00 (0.92-1.09), 0.98 (0.90-1.07), and 0.93 (0.86-1.01), respectively. CONCLUSIONS:These studies demonstrate that BI 853520 can be given with no food restrictions, and as a liquid dispersion, without strongly impacting pharmacokinetics. These pharmacokinetic properties may help make BI 853520 dosing more convenient and flexible, improving treatment compliance. CLINICAL TRIALS REGISTRATION:ClinicalTrials.gov identifier: NCT01335269.

Dataset Information

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

Publications

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

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