Conatumumab, a fully human mAb against death receptor 5 for the treatment of cancer

Conatumumab (AMG-655), under development by Amgen Inc and Japanese licensee Takeda Bio Development Center Ltd, is a fully human IgG1 mAb that binds to the extracellular domain of death receptor 5 (DR5) for the potential intravenous treatment of cancer. In vitro and in vivo studies have demonstrated that conatumumab induces apoptosis in cell lines derived from colon and pancreatic cancers, as well as in mice bearing xenograft tumors. Preclinical studies also indicated that conatumumab enhances the antitumor activity of agents, such as irinotecan and gemcitabine. The results of phase I clinical trials have demonstrated the safety of conatumumab as a monotherapy, as well as in combination with other antibody therapies or standard chemotherapeutic regimes. In addition, anti-conatumumab antibody responses have not been observed in the trials conducted to date. At the time of publication, initial results from phase I/II trials suggest a possible therapeutic role for conatumumab in patients with tumors expressing DR5.