Background: Emerging data suggests that TNBC may be sensitive to DNA-damaging chemotherapy agents, including carboplatin (Cb). Veliparib (V; ABT-888), a potent, competitive poly (ADP-ribose) polymerase (PARP)-1 and -2 inhibitor, enhances the activity of several DNA-damaging agents. In I-SPY2, the addition of V and Cb to standard neoadjuvant therapy for early TNBC doubled the pathologic complete response (pCR) rate (52% vs. 26%). This study will evaluate the addition of Cb or V + Cb to neoadjuvant paclitaxel (P) followed by doxorubicin + cyclophosphamide (AC). Methods: A phase 3, randomized, placebo-controlled, double-blinded, multinational, multicenter study will enroll 624 patients (pts) with histologically confirmed, invasive, TNBC (T2-T4 N0-2 or T1 N1-2) who are candidates for potentially curative surgery. No prior breast cancer treatment or sentinel lymph node biopsy is permitted. Pts will be stratified by BRCA status, lymph node stage (N0 versus N1-2), and schedule of AC administration (q2 weeks versus q3 weeks), and randomized in a 2:1:1 ratio to: (Arm A) P 80 mg/m² weekly + Cb AUC 6 mg/mL/min q3weeks x 4 + V 50 mg PO BID for 12 weeks followed by AC (60 mg/m²/600 mg/m² q2 or 3 weeks x 4); (Arm B) P + Cb + PO placebo followed by AC; (Arm C) P + IV placebo + PO placebo followed by AC. After completing study therapy, pts will undergo surgery with sentinel node sampling or axillary lymph node dissection. Post-op radiotherapy is at MD discretion. The primary objective of the study is to assess the incidence of pCR defined as absence of residual invasive cancer in resected breast tissue and lymph nodes (i.e., ypT0/is N0 per AJCC staging system). Assuming pCR rates in the V + Cb, Cb only and control arms are 60%, 45% and 40%, respectively, the study has > 80% power at 2-sided α level of 0.05 to detect a statistically significant treatment effect in pCR for the V + Cb arm compared to either of the other two arms using chi-square test. Secondary objective is the rate of eligibility for breast conservation after therapy. Other endpoints are residual cancer burden, EFS and OS. The study opened in Jan 2014. Clinical trial information: NCT02032277.