靶向B7-H3的ADC药物GSK5764227在多种实体瘤转化模型中展现出广泛而多样的抗肿瘤活性

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.