GSK5764227: An Antibody-Drug Conjugate Targeting B7-H3 Enters Phase 1/2 Trial

GSK5764227 represents a promising advancement in treating metastatic castration-resistant prostate cancer (mCRPC). This antibody-drug conjugate targets B7-H3, a protein overexpressed on prostate cancer cells, delivering a topoisomerase I inhibitor payload directly to tumors while minimizing damage to healthy tissues. Early data from broader solid tumor studies show the drug’s monotherapy potential, with objective response rates around 60% in heavily pretreated patients across indications, suggesting it could add meaningful activity when combined with existing therapies.​

The newest development specifically for prostate cancer comes from a phase 1b/2 trial, which tests GSK5764227 alongside enzalutamide in patients with histologically confirmed mCRPC. This sequential, non-randomized study enrolls about 72 patients overall, focusing on a dedicated mCRPC cohort where the combination aims to enhance enzalutamide’s androgen receptor blockade with targeted cytotoxicity against B7-H3-positive cells.​

This trial builds on the drug’s half-life of 3-7 days and dose-proportional exposure, positioning it to potentially overcome resistance mechanisms in mCRPC where B7-H3 expression correlates with aggressive disease and poor prognosis. With estimated start in December 2025 and completion by late 2028, results could define a new backbone for post-enzalutamide therapy, especially given the lack of new standards in later-line mCRPC.

Clinical trial.