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Targeted Oncology
Published in: Targeted Oncology 1/2019

Open Access 01-02-2019 | Pharmacodynamics | Original Research Article

Phase I Study of BI 853520, an Inhibitor of Focal Adhesion Kinase, in Patients with Advanced or Metastatic Nonhematologic Malignancies

Authors: Maja J. A. de Jonge, Neeltje Steeghs, Martijn P. Lolkema, Sebastien J. Hotte, Hal W. Hirte, Diane A. J. van der Biessen, Albiruni R. Abdul Razak, Filip Y. F. L. De Vos, Remy B. Verheijen, David Schnell, Linda C. Pronk, Monique Jansen, Lillian L. Siu

Published in: Targeted Oncology | Issue 1/2019

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Abstract

Background

Overexpression/activation of focal adhesion kinase (FAK) in human malignancies has led to its evaluation as a therapeutic target. We report the first-in-human phase I study of BI 853520, a novel, potent, highly selective FAK inhibitor.

Objective

Our objectives were to identify the maximum tolerated dose (MTD), and to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), biomarker expression, and preliminary activity.

Patients and Methods

The study comprised a standard 3 + 3 dose-escalation phase followed by an expansion phase in patients with selected advanced, nonhematologic malignancies.

Results

Thirty-three patients received BI 853520 in the dose-escalation phase; the MTD was 200 mg once daily (QD). Dose-limiting toxicities included proteinuria and fatigue, both of which were grade 3. Preliminary PK data supported QD dosing. In the expansion cohort, 63 patients received BI 853520 200 mg QD. Drug-related adverse events (AEs) in > 10% of patients included proteinuria (57%), nausea (57%), fatigue (51%), diarrhea (48%), vomiting (40%), decreased appetite (19%), and peripheral edema (16%). Most AEs were grade 1–2; grade 3 proteinuria, reported in 13 patients (21%), was generally reversible upon treatment interruption. Nineteen patients underwent dose reduction due to AEs, and three drug-related serious AEs were reported, none of which were fatal. Preliminary PD analysis indicated target engagement. Of 63 patients, 49 were evaluable; 17 (27%) achieved a best response of stable disease (4 with 150 + days), and 32 (51%) patients had progressive disease.

Conclusions

BI 853520 has a manageable and acceptable safety profile, favorable PK, and modest antitumor activity at an MTD of 200 mg QD in patients with selected advanced nonhematologic malignancies.

ClinicalTrials.gov identifier

NCT01335269.
Appendix
Available only for authorised users
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Metadata
Title
Phase I Study of BI 853520, an Inhibitor of Focal Adhesion Kinase, in Patients with Advanced or Metastatic Nonhematologic Malignancies
Authors
Maja J. A. de Jonge
Neeltje Steeghs
Martijn P. Lolkema
Sebastien J. Hotte
Hal W. Hirte
Diane A. J. van der Biessen
Albiruni R. Abdul Razak
Filip Y. F. L. De Vos
Remy B. Verheijen
David Schnell
Linda C. Pronk
Monique Jansen
Lillian L. Siu
Publication date
01-02-2019
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 1/2019
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-018-00617-1

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