Suppression of poly-ADP ribose (PAR) levels in PBMCs by veliparib (vel) as a pharmacodynamic (PD) marker associated with survival among women with BRCA1- or BRCA2- (BRCA)-associated metastatic breast cancer (MBC).

2549Background: PARP inhibitor therapy of BRCA-associated cancer exploits the concept of synthetic lethality, yet there have been limited PD markers of efficacy. We report here on baseline PAR and suppression of PAR in PBMCs as a PD marker of clinical outcome, as well as pharmacokinetics (PK). Methods: Pts received either carboplatin (carb) IV and oral vel (Phase I) or single agent vel (Phase II) followed by post-progression therapy with the combination (NCI protocol #8264; NO1-CM-2011-00038). Blood for PK analysis (phase I only) and PBMCs were collected at baseline, at 3hrs, and at additional later time points. Plasma vel and PAR were quantitated using LC-MS assay and CTEP-validated reagents and methods, respectively. Results: 72 evaluable pts included 28 in Phase I, 44 in Phase II. PK samples were available for 25/28 pts in phase I; vel PK parameters are in line with values previously reported (Cl/F 20.9 L/h, V/F 173 L, t1/2 6.1 h). Response rate (RR) in phase I was 56% [CR rate 15%] and 3 remain in CR ...