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Ref Type Journal Article
PMID (30756308)
Authors de Jonge MJA, Steeghs N, Lolkema MP, Hotte SJ, Hirte HW, van der Biessen DAJ, Abdul Razak AR, De Vos FYFL, Verheijen RB, Schnell D, Pronk LC, Jansen M, Siu LL
Title Phase I Study of BI 853520, an Inhibitor of Focal Adhesion Kinase, in Patients with Advanced or Metastatic Nonhematologic Malignancies.
Journal Targeted oncology
Vol 14
Issue 1
Date 2019 Feb
URL
Abstract Text 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.Our objectives were to identify the maximum tolerated dose (MTD), and to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), biomarker expression, and preliminary activity.The study comprised a standard 3 + 3 dose-escalation phase followed by an expansion phase in patients with selected advanced, nonhematologic malignancies.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.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.NCT01335269.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
BI 853520 IN10018|IN 10018|IN-10018|BI853520|BI-853520 FAK inhibitor 13 BI 853520 is an inhibitor of PTK2 (FAK), which has demonstrated anti-tumor activity, including tumor growth inhibition and regression (Mol Cancer Ther November 2011 10; A249, PMID: 30756308).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown Advanced Solid Tumor not applicable BI 853520 Phase I Actionable In a Phase I trial, BI 853520 demonstrated safety and some anti-tumor efficacy, resulting in stable disease in 27% (17/63) of patients with advanced solid tumors (PMID: 30756308; NCT01335269). 30756308
Unknown unknown ovarian carcinoma not applicable BI 853520 Phase I Actionable In a Phase I trial, BI 853520 demonstrated safety and some anti-tumor efficacy, resulting in stable disease in 31% (5/16) of patients with platinum-resistant ovarian carcinoma, one of whom had stable disease lasting greater than 150 days (PMID: 30756308; NCT01335269). 30756308
Unknown unknown sarcoma not applicable BI 853520 Phase I Actionable In a Phase I trial, BI 853520 demonstrated safety and some anti-tumor efficacy, resulting in stable disease in 28.6% (4/14) of patients with soft tissue sarcoma, one of whom had stable disease lasting greater than 150 days (PMID: 30756308; NCT01335269). 30756308
Unknown unknown esophageal carcinoma not applicable BI 853520 Phase I Actionable In a Phase I trial, BI 853520 demonstrated safety and some anti-tumor efficacy, resulting in stable disease in 12.5% (2/16) of patients with esophageal carcinoma (PMID: 30756308; NCT01335269). 30756308
Unknown unknown pancreatic adenocarcinoma not applicable BI 853520 Phase I Actionable In a Phase I trial, BI 853520 demonstrated safety and some anti-tumor efficacy, resulting in stable disease in 35% (6/17) of patients with pancreatic adenocarcinoma, two of whom had stable disease lasting greater than 150 days (PMID: 30756308; NCT01335269). 30756308