Final results of a phase 1 study of single-agent veliparib (V) in patients (pts) with either BRCA1/2-mutated cancer (BRCA+), platinum-refractory ovarian, or basal-like breast cancer (BRCA-wt).

2570 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 occurr...