Abstract 1806: Efficacy of MM121 in ER+ and triple negative breast cancer studies

Abstract

Abstract In women, breast cancer is among the most common cancers and the fifth most common cause of cancer deaths. Due to the heterogeneity of the disease, 10-year progression free survival can vary widely with stage and type from 98% to 10%. We present data showing that MM-121, a fully human monoclonal anti-ErbB3 antibody, is efficacious in studies of both hormone dependent (ER+) and triple negative (ER-,PR-, Low Erb2) breast cancer lines that express the molecular profile consistent with MM-121 response (co-expression of ErbB3 and HRG). Using a combination of computational and experimental approaches, ErbB3 was identified as a critical transducer of oncogenic signaling leading to the development of MM-121, a first in class anti-ErbB3 antibody. We have previously demonstrated that MM-121, when used as a single agent, inhibits heregulin-induced signaling events in human cancer cell lines. Moreover, MM-121 caused dose-dependent inhibition of tumor growth in multiple xenograft models of human cancer, including ovarian, renal cell, pancreatic, lung, and prostate cancer. Estrogen dependent, or ER+ breast cancers, make up about 80% of breast cancers. A standard treatment for ER+ breast cancer includes hormone therapy; however a substantial number of ER+ breast cancers eventually develop resistance requiring additional treatments. Here we show that in ER+ breast cancer cells, MM-121 can block HRG induced ErbB3 activation and VEGF secretion as well as HGF induced pErbB3 in vitro. Additionally, in ER+ breast cancer xenograft models, MM121 is effective in combination with both chemotherapy agents and targeted therapies and may be effective in ER+ breast cancers that are refractory to hormone treatment. The triple negative breast cancers are characterized by poor prognosis, aggressiveness, and reduced responsiveness to standard treatments. MM-121 used as a single agent therapy was able to suppress tumor growth in triple negative primary human tumors, when grown as xenografts suggesting that MM-121 monotherapy may be clinically efficacious in triple negative breast cancers. Together, these data suggest that MM-121, when used as a single agent or in combination with other therapies, could offer significant clinical benefit to both ER+ and triple negative breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1806.