Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) have activity in tumors with DNA repair defects, including BRCA 1/2 deficient cancers. CP is synergistic with the PARPi veliparib in xenografts, and has anti-tumor activity in TNBC and BRCA1 deficient breast cancer. VNR shows preclinical synergy with CP and the combination has efficacy in metastatic breast cancer (MBC). We hypothesize that veliparib combined with CP and VNR is active in TNBC and will be most effective in tumors with DNA repair defects. Methods: To determine maximum tolerated dose (MTD), pharmacokinetic (PK) and pharmacodynamic profiles, and anti-tumor activity, patients (pts) with TNBC and/or BRCA1/2+ MBC received CP 75 mg/m² day 1, VNR 25 mg/m²days 1, 8 and escalating doses of veliparib (V) orally BID days 1-14, every 21 days for 6-10 cycles followed by maintenance V. Results: 45 pts enrolled in 9 cohorts. Treatment was tolerated well; MTD was not reached. 36 pts (80%) had at least 1 prior metastatic regimen (range 1-11). BRCA mutation status was: BRCA1+ (n=9); BRCA2+ (n=3); negative (n=24); unknown (n=9). BID V dose cohorts were: 20 mg (n=4); 30 mg (n=3); 40 mg (n=6); 60 mg (n=8); 80 mg (n=5 ); 120 mg (n=6); 160 mg (n=3); 200 mg (n=7); and 300 mg (n=3). DLT occurred at 40 mg BID in 1 pt with grade (gr) 4 thrombocytopenia, 60 mg BID (gr 4 neutropenia + fever, n=1), and 200 mg BID (gr 3 neutropenia + fever, n=1). Most common adverse events (AEs) were nausea, anemia, fatigue, mainly gr 1/2. Most common gr 3/4 AEs were neutropenia (n=13), anemia (n=11), thrombocytopenia (n=6). Of 38 evaluable pts, 21 (55%) responded (2 CR, 19 PR), 13 (34%) had SD, and 4 had PD, as best response. One pt with CR remains on trial for 42+ cycles. Response was 73% in BRCA 1/2+ pts (6/11 PR; 2/11 CR), 53% in BRCA1/2- pts (11/21 PR) and 33% in unknown status pts (2/6 PR). Analyses of PK and correlative predictors of response will be presented. Conclusions: Veliparib at the recommended phase II dose of 300mg BID combined with CP and VNR is well tolerated. BRCA mutation carriers and pts with sporadic TNBC, including heavily pretreated pts, responded. We plan to investigate the contribution of veliparib to cisplatin-based therapy in a randomized trial. Clinical trial information: NCT01104259.