SOPHIA: A phase 3, randomized study of margetuximab (M) plus chemotherapy (CTX) vs trastuzumab (T) plus CTX in the treatment of patients with HER2+ metastatic breast cancer (MBC).

Abstract

TPS630Background: Despite significant advances in targeted therapy, HER2+ MBC remains incurable. Ideal treatment includes pertuzumab (P) and T in combination with a taxane in the first line setting, followed by ado-trastuzumab emtansine (K) on progression. Optimal treatment regimens in the > third line of therapy are not defined, but continued anti-HER2 therapy is recommended. m is a Fc-modified monoclonal antibody (Mab) to HER2 that recognizes the same epitope on HER2 as does T with similar affinity. m demonstrates increased affinity to the activating CD16A Fc-receptor found on NK cells and macrophages and decreased affinity to the inhibitory CD32B receptor compared to T. In vitro studies showed enhanced antibody dependent cell-mediated cytotoxicity compared to T. In a phase I dose expansion trial, m showed single agent clinical activity against HER2+ tumors in patients previously treated with T and other anti-HER2 agents. Methods: SOPHIA is a randomized, prospective study testing the hypothesis that m p...