Abstract 1197: A multi tumor survey of Nectin-4 expression to guide BT8009 indication selection

Introduction: Bicycles® are a novel class of fully synthetic, short, constrained peptides. BT8009 consists of a bicyclic peptide targeting the tumor antigen Nectin-4, linked to the cytotoxin monomethyl auristatin E (MMAE) via a molecular spacer and cleavable linker. Nectin-4 is a validated tumor target and is highly expressed in a wide range of tumors. A Phase I/II dose escalation/expansion study, BT8009-100 (NCT04561362), enrolling patients with advanced solid tumors associated with Nectin-4 expression is ongoing in the US. Here we report the analysis of tumor tissue microarrays (TMAs) stained with a Nectin-4 immunohistochemistry (IHC) assay to support patient selection for the BT8009-100 study. Methods: We developed a clinical grade Nectin-4 IHC assay on the Leica platform using a proprietary rabbit monoclonal α-Nectin-4 primary antibody (Abcam, Burlingame, CA) and the BOND Polymer Refine detection kit. TMAs of cancer types reported to have high Nectin-4 expression, including esophageal, pancreatic, bladder, head & neck, stomach, non-small cell lung, breast, and ovarian cancer, were stained and manually scored for Nectin-4 levels, with the tumor microenvironment evaluated in a subset of samples. Nectin-4 H-scores (stain intensity on a scale of 0-3 x percent positive tumor cells) were generated by a pathologist independently for tumor cell membrane and tumor cytoplasm. H-scores ≥ 100 in the tumor membrane or cytoplasm were considered positive. Results: In all indications tested, a greater degree of Nectin-4 positivity was observed in the tumor cytoplasm as compared to tumor membrane. Breast and bladder cancer had the greatest frequency of Nectin-4 positivity. Subtype analysis in breast cancer identified enrichment of Nectin-4 expression in hormone receptor negative and human epidermal growth factor receptor 2 positive tumors.

Conclusion: The frequency of Nectin-4 expression as measured by IHC across multiple tumor types may guide clinical strategy for the BT8009 program.

Citation Format: Carly T. Campbell, Robert Smale, Michael Rigby, Shawn Watson, Amy Dickson, Tara Gelb, Heather Cohen, Pierre Lee, Josette William Ragheb, Stephen J. Blakemore. A multi tumor survey of Nectin-4 expression to guide BT8009 indication selection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1197.