Background: Veliparib (V) (ABT-888) is a potent, oral PARP 1/2 inhibitor with preclinical and clinical efficacy in BRCA+ malignancies. As there are known similarities between BRCA+ cancers, serous ovarian cancer, and basal-like breast cancer, we postulated potential for V activity in these groups also. We sought to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetic (PK) and pharmocodynamic properties, and preliminary efficacy of chronically-dosed V. Methods: A 3+3 dose-escalation phase I trial was performed. Nine dose levels ranging from 50 mg BID to 500 mg BID dosed continuously were enrolled to determine a maximum tolerated dose (MTD) and recommended phase II dose (RP2D). A biopsy cohort in BRCA+ patients was enrolled at the RP2D. Correlative studies included assessment of BRCA reversion mutation analysis, DNA repair pathway analysis, and BRCA promoter methylation status. Results: A total of 88 pts (60 BRCA+ and 28 BRCA-wt) were enrolled to date. DLTs occurred at the following dose levels: BRCA+: gr 3 nausea/vomiting at 400 mg BID, gr 2 seizure at 500 mg BID; BRCA-wt: gr 2 seizure at 400 mg BID. The RP2D was established at 400 mg BID. The most common all-grade toxicities were nausea, fatigue, and lymphopenia. PK was linear and non-saturable with t ½ of 5.2 h. Fifty-two BRCA+ patients (28 ovary, 13 breast, 11 other) were evaluable for response. In BRCA+ patients at all dose levels, the ORR (CR+PR) was 23% with a clinical benefit rate (CBR; CR + PR + stable disease) of 58%. At the MTD and RP2D, 28 BRCA+ patients were evaluable, with an ORR of 40%, and a CBR of 68%. Twenty-four BRCA-wt pts (21 breast and 3 ovary) were evaluable for response, and the ORR was 4% with a CBR of 38%. Conclusions: Single-agent V is well-tolerated with evidence of anti-tumor activity seen in both BRCA+ and BRCA-wt tumors comparable to other single agent PARP inhibitors. Evidence of potential dose responsiveness was observed. Correlative studies from archival tissues and mandatory biopsy cohort, with final data to be presented, will provide early insights on potential mechanisms of response and resistance. Clinical trial information: NCT00892736.