BMN-673 Poly [ADP-ribose] Polymerase (PARP) Inhibitor Oncolytic

Poly [ADP-ribose] polymerase (PARP) inhibitors display cytotoxicity in BRCA-1/2-deficient cells, which is why they were moved into clinical practice as anticancer agents, particularly in BRCA-mutated breast and ovarian cancers. BMN-673 (LT-00673) is a new, orally active, highly potent PARP-1/2 inhibitor, currently in phase III trials for the treatment of germline BRCA-mutated advanced and/or metastatic breast cancer, and in early clinical development for the treatment of solid tumors and advanced hematological malignancies. In preclinical studies it showed antiproliferative and antitumor activity as a single agent and enhanced the cytotoxicity of alkylating agents and radiotherapy in human cancer cell lines and human tumor murine xenografts carrying BRCA-1/2 or PTEN natural mutations, with high selectivity for BRCA-mutated cancer cells over wild-type cells. In a phase I trial in 77 cancer patients, BMN-673 was well tolerated and displayed high antitumor activity in heavily pre-treated ovarian and breast cancer patients with BRCA mutations.