Cancers, Vol. 11, Pages 1987: Phase 1 Dose Escalation Study of the Allosteric AKT Inhibitor BAY 1125976 in Advanced Solid Cancer —Lack of Association between Activating AKT Mutation and AKT Inhibition-Derived Efficacy

Cancers, Vol. 11, Pages 1987: Phase 1 Dose Escalation Study of the Allosteric AKT Inhibitor BAY 1125976 in Advanced Solid Cancer—Lack of Association between Activating AKT Mutation and AKT Inhibition-Derived Efficacy Cancers doi: 10.3390/cancers11121987 Authors: Andreas Schneeweiss Dagmar Hess Markus Joerger Andrea Varga Stacy Moulder Apostolia M. Tsimberidou Cynthia Ma Sara A. Hurvitz Christine Rentzsch Marion Rudolph Silke Thiele Oliver Boix Gary Wilkinson Eleni Lagkadinou Matthias Ocker This open-label, phase I first-in-human study (NCT01915576) of BAY 1125976, a highly specific and potent allosteric inhibitor of AKT1/2, aimed to evaluate the safety, pharmacokinetics, and maximum tolerated dose of BAY 1125976 in patients with advanced solid tumors. Oral dose escalation was investigated with a continuous once daily (QD) treatment (21 days/cycle) and a twice daily (BID) schedule. A dose expansion in 28 patients with hormone receptor-positive metastatic breast cancer, including nine patients harboring the AKT1E17K mutation, was performed at the recommended phase 2 dose (R2D) of 60 mg BID. Dose-limiting toxicities (Grades 3–4) were increased in transaminases, γ-glutamyltransferase (γ-GT), and alkaline phosphatase in four patients in both schedules and stomach pain in one patient. Of the 78 patients enrolled, one patient had a partial response, 30 had stable disease, and 38 had progressive disease. ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research