Final Results Of A Translational Phase L Study Assessing A Qod Schedule Of The Potent Akt Inhibitor Mk-2206 Incorporating Predictive, Pharmacodynamic (Pd), And Functional Imaging Biomarkers.

3001^ Background: MK-2206 is a novel allosteric inhibitor of all 3 isoforms of AKT, which are targets implicated in malignant progression. Methods: The investigational agent MK-2206 was given orally QOD to patients (pt) with advanced solid tumors. PD studies of AKT and downstream protein phosphorylation (p) were carried out in tumor biopsies and platelet-rich plasma with MesoScale Discovery (MSD) ELISA, and hair follicles with immunofluorescence. Tumor biopsies were sequenced with Sequenom Oncocarta panel for putative predictive biomarkers and stained with IHC for PTEN expression. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), MR spectroscopy (MRS) and diffusion weighted imaging (DWI) were conducted. Results: 71 pt (37 M; median age 59y; ECOG PS 0/1: 22/49) received MK-2206 at 30, 60, 75, 90 mg QOD. G3 rash (n=6) was dose limiting at 75-90 mg QOD, establishing MTD at 60mg QOD. Four MTD expansion cohorts were then undertaken: paired tumor biopsies (n=14), functional imaging (n=13), ovarian...