Abstract 2832: Development of AGS-22M6E, a novel antibody drug conjugate (ADC) targeting Nectin-4 for the treatment of solid tumors

Abstract

Abstract Nectin-4 is a type I transmembrane antigen identified by Agensys to be highly expressed at the RNA level in a significant number of bladder and breast cancer specimens. Analysis of protein expression carried out in an extensive panel of tumor specimens by immunohistochemistry confirmed strong to moderate expression levels of Nectin-4 in bladder, breast and pancreatic cancers (40-60%). A subset of lung and ovarian cancers (up to 30%) also showed significant expression levels of this protein. We have generated an antibody-drug conjugate (ADC) targeting Nectin-4, AGS-22M6E. The highly potent microtubule disrupting drug monomethyl auristatin E (MMAE) was conjugated via valine-citrulline cleavable linker to a fully human IgG1k antibody specific for Nectin-4. AGS-22M6E was characterized for binding affinity, species crossreactivity and cytotoxicity in vitro. AGS-22M6E binds to cell surface Nectin-4 with high affinity and crossreacts with Nectin-4 orthologs of cynomolgus monkey, rat and murine origin. Upon binding to its target on the cell surface AGS-22M6E is internalized and induces cell death in vitro in a dose dependent manner. In vivo efficacy of AGS-22M6E was tested in SCID mice on xenograft models of breast, bladder, pancreatic and lung cancers in subcutaneous and orthotopic modalities. Treatment of well established tumor xenografts with the ADC resulted in significant growth inhibition or complete eradication of tumors in various models covering multiple cancer indications. Pharmacokinetics of AGS-22M6E in non-tumor bearing mice was also evaluated and will be discussed. Overall, these data validate AGS-22M6E as an attractive therapeutic drug candidate for multiple solid tumor indications and support further clinical investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2832. doi:10.1158/1538-7445.AM2011-2832