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Antibody-drug conjugates (ADCs) targeting B7-H4 are showing impressive early results in endometrial and ovarian cancers, with response rates exceeding 60%. Two development strategies — one biomarker-directed, one not — are both showing similar efficacy so far. Experts see potential for these agents to move into frontline therapy and combine with immunotherapy.
Antibody-drug conjugates (ADCs) targeting a protein called B7-H4 are generating buzz in gynecologic oncology, with early trial data showing strong response rates in both endometrial and ovarian cancers. B7-H4 is highly expressed across these tumor types, making it an attractive therapeutic target.
Two agents are leading the charge: mocertatug rezetecan (GSK5733584) and puxitatug samrotecan (AZD8205). Developers are taking different approaches — one drug is being tested regardless of B7-H4 expression levels, while the other requires patients to meet a minimum expression threshold. So far, efficacy looks comparable between the two strategies.
Beyond strong response rates, these ADCs appear more tolerable than others in their class, with lower rates of mucositis and fatigue. Researchers are also eyeing their potential in frontline therapy and in combination with immunotherapy, with emerging data suggesting they may help overcome resistance to PARP inhibitors.
By the Numbers
Why it matters: With limited options for patients with recurrent gynecologic cancers, B7-H4–directed ADCs could represent a meaningful step forward — both as later-line salvage therapy and potentially as a backbone of frontline treatment regimens.
