A phase 3 study of the oral PARP inhibitor talazoparib (BMN 673) in BRCA mutation subjects with advanced breast cancer (EMBRACA)

Abstract

BACKGROUND: Poly-ADP-ribose polymerase (PARP) enzymes are important in DNA repair. PARP inhibition induces lethality in tumor cells with mutations in the genes encoding breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2). Talazoparib (BMN 673) is a novel, dual-mechanism PARP inhibitor that both potently inhibits the PARP enzyme and effectively traps PARP on DNA, resulting in cell death in BRCA1/2-mutated cells.[1, 2] Talazoparib has shown promising single-agent antitumor efficacy in several solid tumor types and generally well tolerated in an ongoing Phase 1/2 clinical study[3]. METHODS: This multi-center, global, Phase 3 trial (EMBRACA) compares the safety and efficacy of talazoparib versus physician's choice treatment (capecitabine, eribulin, gemcitabine or vinorelbine) in locally advanced and/or metastatic breast cancer subjects with germline BRCA mutations. The primary study objective is to evaluate progression-free survival (PFS) in subjects treated with talazoparib as a monotherapy compared with those treated with protocol-specific physician's choice. Secondary objectives include objective response rate (ORR), overall survival (OS), and safety. Patients may be eligible if they are >/=18 years, have histologically/cytologically confirmed breast carcinoma, locally advanced and/or metastatic disease, documentation of a deleterious or pathogenic germline BRCA1 or BRCA2 mutation,