Abstract 675: B7-H3 targeting ADC GSK5764227 demonstrates broad and varied anti-tumor activity across solid tumor translational models.

Abstract B7-H3 (B7 homolog 3 protein), also known as CD276 (cluster of differentiation 276), is a cell surface protein that is over-expressed across multiple solid tumors. B7-H3 suppresses T-cell function (e.g. proliferation, activation, and cytokine release) to promote tumorigenesis. Due to its tumor-promoting functions and broad expression profile on a range of malignancies, B7-H3 is an attractive therapeutic target for antibody-drug conjugates (ADCs). GSK5764227 is a B7-H3 targeting ADC conjugated to a topoisomerase I (TOPO1) inhibitor payload, with a DAR of 4. Here we demonstrate in vitro and in vivo efficacy data of GSK5764227 in different preclinical models - including cell lines, in vitro patient-derived organoids (PDOs), and in vivo patient-derived xenografts (PDX) - across multiple tumor indications including lung, bladder, pancreatic, colorectal (CRC), uterine, prostate, and gastric cancers, supporting the broad therapeutic potential of GSK’227 across different malignancies. Activity was highly varied across tumor histologies in cell lines and PDO models. Similarly, responses were observed across a wide range of PDX indications, but depth of response varied among models within indications. These findings underscore the promise of B7-H3 targeting ADCs with topoisomerase payloads for treating a broad range of cancers, while highlighting the need for further exploration of patient population and/or predictive biomarkers to elucidate determinants of response. Together, this work supports GSK5764227 ongoing clinical development as an innovative therapeutic strategy to address unmet patient needs. Citation Format: Michael Adam, Miriam Doepner, Ning Sun, Chris Hopson, Derek Poore, Prajna Behera, Jenny Laraio, Anthony Mazurek, Andrew Gehman, Shannon McKearnan, Jacob Parsons, Bjoern-Philipp Kloke, Shoba Shetty, Ken Hance, Jeremy Waight, Klaas Bakker. B7-H3 targeting ADC GSK5764227 demonstrates broad and varied anti-tumor activity across solid tumor translational models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 675.