GSK-5733584: A Comprehensive Analysis of a Novel B7-H4-Targeted Antibody-Drug Conjugate in Oncology

I. Executive Summary

[GSK-5733584 is an investigational new molecular entity poised to address significant unmet medical needs in advanced solid tumors, particularly within gynecologic oncology. Developed by Hansoh Pharma and licensed by GSK for global development, this agent is an antibody-drug conjugate (ADC) meticulously engineered to target B7-homolog 4 (B7-H4), a transmembrane protein overexpressed on numerous cancers with limited presence in healthy tissues. Its architecture comprises a humanized anti-B7-H4 IgG1 monoclonal antibody, a stable protease-cleavable linker, and a potent topoisomerase-1 inhibitor (TOP1i) payload, rezetecan, with a high drug-to-antibody ratio of 6. This design facilitates the targeted delivery of a cytotoxic agent directly to cancer cells, leading to DNA damage and apoptosis.]

[The clinical development program for GSK-5733584 is robust and strategically focused. Building on promising initial data from a first-in-human Phase 1 study in China (NCT05263479), GSK has launched a global, multiregional Phase 1/2 study, BEHOLD-1 (NCT06431594). This pivotal trial is designed not only to establish a safe and effective dose but also to evaluate clinical activity in dedicated expansion cohorts of heavily pre-treated patients with platinum-resistant ovarian cancer (PROC) and advanced/recurrent endometrial cancer (EC). A subsequent Phase 1/2 study, BEHOLD-2 (NCT06796907), will explore its potential in combination with other anti-cancer therapies.]