B7 Homolog 4 (B7-H4)-Directed Agents in Oncology Clinical Trials: A Review

Abstract

B7 homolog 4 (B7-H4) is a transmembrane protein found on immune cells and is frequently overexpressed in various solid tumors, making it a promising target for cancer therapy. B7-H4–directed agents, particularly antibody-drug conjugates (ADCs) like puxitatug samrotecan (AZD8205), felmetatug vedotin (SGN-B7H4V), and GSK5733584, have demonstrated early clinical activity with promising response rates in triple-negative breast cancer (TNBC). Combination strategies, such as ADCs with anti–PD-1 or PARP inhibitor therapies, have also shown enhanced tumor regression in preclinical models and are the subject of several ongoing clinical trials. This review highlights the current landscape of B7-H4–targeted agents, their progress in clinical trials, and the potential for combination approaches to improve outcomes in B7-H4–expressing cancers.

Keywords

• b7-h4
• cancer
• clinical trials