Background: Poly-ADP-ribose polymerase (PARP) represents a family of enzymes of which at least two (PARP1 and PARP2) play important roles in DNA repair. PARP inhibition induces synthetic lethality in tumor cells bearing deleterious mutations in the genes BRCA1/2. Talazoparib (BMN 673) is a novel, dual-mechanism PARP inhibitor that potently inhibits the PARP enzyme and effectively traps PARP on DNA [1]. In preclinical models, trapping PARP on DNA was more likely to induce cancer cell death than inhibition of PARP alone [1,2]. Talazoparib is the most potent preclinical PARP inhibitor described to date with the highest efficiency at trapping PARP-DNA complexes [1]. Talazoparib has shown promising single-agent anti-tumor efficacy in several solid tumor types and was generally well tolerated in a Phase 1/2 clinical study [3]. Methods: This Phase 2 trial (ABRAZO) evaluates the safety and efficacy of talazoparib in patients with locally advanced or metastatic breast cancer with a deleterious germline BRCA 1 or BRCA 2 mutation. Eligible subjects will be assigned to one of two cohorts: 1) Subjects (n = 70) previously responding to a platinum-containing regimen for metastatic disease (PR or CR) or 2) Subjects (n = 70) with > 2 prior chemotherapy regimens in metastatic setting, no prior platinum therapy. The primary objective is objective response rate (ORR). Secondary objectives include clinical benefit rate (CBR), duration of response (DOR), progression free survival (PFS), and overall survival (OS). Health-related quality of life assessments are an exploratory objective. Patient eligibility includes ≥ 18 years, locally advanced and/or metastatic disease, deleterious BRCA1/2 mutation, and ECOG performance status ≤ 1. Eligible patients will receive oral talazoparib (1.0 mg/day, 21-day cycles) until disease progression or unacceptable toxicity. This trial is enrolling patients in the United States, France, Germany, Spain, and the United Kingdom. (NCT02034916). [1] Murai J et al. Cancer Res. 2012;72(21):5588-5599. [2] Murai J et al. Mol Cancer Ther. 2014;13:433-443. [3] Wainberg ZA et al. J Clin Oncol. 2014;32(suppl):5; abstr 7522 Clinical trial information: NCT02034916