Early-Phase Study Shows Promise for Novel B7-H4–Targeted ADC

Emiltatug ledadotin (Emi-Le; XMT-1660), a novel B7-H4-directed dolasynthen antibody-drug conjugate (ADC), demonstrated promising antitumor activity and a manageable safety profile in a phase 1 dose-escalation trial presented at the 2025 American Society of Clinical Oncology (ASCO) 2025 Annual Meeting.

B7-H4 is an immune checkpoint protein overexpressed in several epithelial cancers, including triple-negative breast cancer (TNBC), hormone receptor–positive breast cancer, endometrial and ovarian cancers, and adenoid cystic carcinoma. The limited expression of B7-H4 in normal tissues makes it an attractive target for therapeutic development, especially in tumor types where treatment options may be limited after progression on standard regimens.

This ongoing trial enrolled patients with advanced or metastatic disease across multiple tumor types. Participants received emiltatug ledadotin in escalating dose tiers to evaluate safety, tolerability, and preliminary signals of antitumor activity. The study included patients who had previously received a range of systemic therapies, including other ADCs, which provides a real-world insight into the potential utility of this approach in heavily pretreated populations.

The design of the trial followed a traditional 3+3 dose escalation model. Investigators assessed adverse events, dose-limiting toxicities, and pharmacokinetics, alongside early indicators of clinical response. The study team noted particular interest in responses seen among patients with rare tumor types, as well as those who had exhausted other ADC options.

As the oncology field continues to expand its ADC pipeline, agents like emiltatug ledadotin may offer new hope for patients with difficult-to-treat cancers. Future phases of the study are expected to further refine dosing and explore efficacy across broader patient populations. Researchers anticipate additional data to inform next steps for clinical development and to better understand which patients may derive the most benefit from this targeted approach.

REFERENCE:

Hamilton EP, Han HS, Kalinsky K, et al. Initial phase 1 dose escalation data for emiltatug ledadotin (Emi-Le), a novel B7-H4-directed dolasynthen antibody-drug conjugate. J Clin Oncol. 2025;43(suppl_16):3009. doi:10.1200/JCO.2025.43.16_suppl.3009