Background: 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 patients (pts) will be enrolled, randomized in a 1:1 ratio, and stratified by PTEN status, node involvement, and tumor size. Pts will receive 3 cycles (each cycle is 28 days) of ipat 400 mg or placebo orally once daily on Days 1 to 21 along with pac 80 mg/m² on Days 1, 8, 15, and 22. All pts will undergo pretreatment and Cycle 1 Day 8 tumor tissue biopsies to evaluate pathway biomarkers. Following three cycles of treatment, pts will undergo surgery. The primary efficacy endpoint is pCR within the breast and axilla (ypT0/Tis ypN0) in all pts and in pts with PTEN-low tumors, and will be assessed by local pathologic assessment. Additional endpoints include objective response rate, safety, BCS rate, pharmacokinetics, and pathway biomarkers. Following surgical resection of primary tumor, pts may continue post-operative treatment with a standard adjuvant chemotherapy regimen at the treating physician’s discretion. As of 14 Jan 2016, 61 patients have been enrolled, and global enrollment is ongoing. Clinical trial information: NCT02301988