Background: TNBC often exhibits activation of PI3K/Akt signaling, associated with loss of PTEN expression, low INPP4B expression, and/or increased AKT3 amplification. Inhibition of the PI3K/Akt pathway in diverse cancers leads to radiosensitization and/or chemosensitization. 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 diverse chemotherapy regimens 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 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 of Ipat or placebo 400 mg orally once daily on Days 1 to 21 of each 28-day cycle, along with pac 80 mg/m² every 7 days for a total of 12 doses. All patients will undergo pretreatment and Day 8 tumor tissue acquisition to evaluate pathway biomarkers. Following three cycles of treatment, patients will undergo surgery. The primary efficacy endpoint, pCR within the breast and axilla (ypT0/Tis ypN0) in all patients and in patients with PTEN-low tumors, will be assessed by local pathology evaluation following completion of neoadjuvant therapy and surgery. Additional endpoints include objective response rate, safety, BCS rate, pharmacokinetics, and pathway biomarkers. Following surgical resection of primary tumor, patients are expected to continue post-operative treatment with a standard adjuvant chemotherapy regimen at physician’s discretion. The study is open for accrual. Clinical trial information: NCT02301988