Presurgical evaluation of the AKT inhibitor MK-2206 in patients with operable invasive breast cancer.

2613 Background: The PI3K/Akt signaling pathway is an important signaling pathway in breast cancer (BC). MK-2206 is the first allosteric Akt inhibitor in clinical development. The purpose of this pre-surgical study is to determine the biologic effects of MK-2206 on tumor and blood markers in newly diagnosed operable BC. Methods: In this trial, 2 doses of weekly MK-2206 were administered in pts with stage I-III invasive BC (at least T1c): first dose at day -9 and second at day -2 from surgery (goal n=30). The primary endpoint was reduction of pAktSer473. Secondary endpoints included change in downstream proteomic changes, tumor proliferation (ki-67), and blood based-markers [phospho-markers in peripheral blood mononuclear cells (PBMCs)]. To maintain tumor quality, samples were processed rapidly by a standardized protocol. Paired t-tests were used to compare biomarker changes before and after MK-2206. Results: From 8/11-3/13, 12 pts were enrolled. The mean age was 53.1 years (SD: 11.2). At diagnosis, the me...