FAIRLANE: A phase II randomized, double-blind, study of the Akt inhibitor ipatasertib (GDC-0068) in combination with paclitaxel as neoadjuvant treatment for early stage triple-negative breast cancer.

Abstract

TPS1105Background: TNBC often exhibits activation of PI3K/Akt signaling, associated with loss of PTEN expression, low INPP4B expression, PI3K/Akt mutations, or PI3K/AKT3 amplification. Inhibition of the PI3K/Akt pathway may lead to radiosensitization and/or chemosensitization. Ipatasertib (ipat) is an oral, potent ATP-competitive small molecule inhibitor of all three isoforms of Akt. The combination of ipat with taxanes in preclinical models resulted in enhanced efficacy relative to either ipat or chemotherapy alone. In a Phase Ib clinical study, the combination of ipat with either paclitaxel (pac) or docetaxel was well-tolerated and resulted in RECIST responses, particularly pts with tumors having PI3K/Akt activation. Methods: FAIRLANE is a randomized, double-blind, placebo-controlled, multicenter, neoadjuvant Phase II study designed to estimate the efficacy of ipat combined with pac versus placebo combined with pac in women with Stage Ia-IIIa triple-negative breast cancer (TNBC). Approximately 150 patie...