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Ref Type Journal Article
PMID (26650227)
Authors Schöffski P, Aftimos P, Dumez H, Deleporte A, De Block K, Costermans J, Billiet M, Meeus MA, Lee C, Schnell D, Goeldner RG, Awada A
Title A phase I study of two dosing schedules of oral BI 847325 in patients with advanced solid tumors.
Journal Cancer chemotherapy and pharmacology
Vol 77
Issue 1
Date 2016 Jan
URL
Abstract Text This study determined the safety, maximum tolerated dose (MTD), pharmacokinetics, and preliminary efficacy of BI 847325, an oral dual MEK and Aurora kinase inhibitor, in patients with refractory solid tumors.This trial recruited patients with an advanced non-resectable and/or metastatic solid tumor following failure of conventional treatment (NCT01324830; 1287.1). BI 847325 was administered orally, once daily (starting at 6 mg in the first cohort) using two dosing schedules: Schedule A (2 weeks on, 1 week off) and Schedule B (three periods of 5 days on, 2 days off). The primary objective was to identify the MTD of BI 847325 for both dosing schedules.Sixty-nine patients (Schedule A, n = 47; Schedule B, n = 22) were treated. The MTD was 120 mg per day for Schedule A (cumulative dose of 1680 mg per 3-week cycle) and 150 mg per day for Schedule B (cumulative dose of 2250 mg per 3-week cycle). Reversible hematologic and gastrointestinal toxicities were the most common dose-limiting toxicities. One patient with esophageal cancer (receiving 160 mg BI 847325, Schedule A) experienced a partial response for 67 days, and 21 patients (n = 11 [23.4%], Schedule A; n = 10 [45.5%], Schedule B) had stable disease. Pharmacokinetic analyses showed at least bi-exponential disposition, with high inter-subject variability. There was no obvious relationship between markers of MEK or Aurora kinase inhibition and exposure to BI 847325 (exploratory analysis).This first-in-human trial suggests that BI 847325 has an acceptable safety profile. However, due to insufficient drug exposure at the MTD to achieve relevant MEK inhibition, a decision was taken to halt the development of BI 847325.

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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
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 esophageal cancer not applicable BI-847325 Phase I Actionable In a Phase I trial, BI-847325 treatment resulted in stable disease in 30% (21/69) of patients with advanced solid tumors, and one partial response for 67 days in a patient with esophageal cancer (PMID: 26650227). 26650227
Unknown unknown Advanced Solid Tumor not applicable BI-847325 Phase I Actionable In a Phase I trial, BI-847325 treatment resulted in stable disease in 30% (21/69) of patients with advanced solid tumors, and one partial response for 67 days in a patient with esophageal cancer (PMID: 26650227). 26650227