A Phase 3, Open-Label, Randomized, Parallel, 2-Arm International Study Of The Oral Parp Inhibitor Talazoparib (Bmn 673) In Brca Mutation Subjects With Locally Advanced And/Or Metastatic Breast Cancer (Embraca).

TPS1107 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 international Phase 3 trial (EMBRACA) compares the safety and efficacy of talazoparib versus physician’s choice (capecitabine, eribulin, gemcitabine or vinorelbine) ...