FDA Grants Breakthrough Therapy Designation to Emiltatug Ledadotin for Adenoid Cystic Carcinoma

The FDA has granted a breakthrough therapy designation to emiltatug ledadotin (emi-le) for the treatment of patients with locally advanced, recurrent or metastatic adenoid cystic carcinoma (ACC) with solid histology or high-grade transformation, according to Servier, the developer of the B7-H4–directed antibody-drug conjugate.¹

The breakthrough designation is supported by initial data from a multicenter phase 1 trial (NCT05377996) exploring the efficacy and safety of emi-le as a single agent in adult patients with ACC, triple-negative breast cancer (TNBC), hormone receptor–positive/HER2-negative breast cancer, ovarian cancer, or endometrial cancer.

During the dose-escalation phase of the study, patients received emi-le at doses ranging from 7.2 to 115 mg/m² per cycle. Data generated across dose levels were used to establish the recommended regimens for the expansion phase. Retrospective immunohistochemistry analyses were performed to assess tumor B7-H4 expression, with a preliminary threshold for high expression defined as a tumor proportion score (TPS) of at least 70.²

Initial results from the phase 1 study presented at the 2025 ASCO Annual Meeting showed that antitumor activity appeared to be associated with both emi-le dose intensity and B7-H4 expression level. Among evaluable patients with high B7-H4 expression treated in the intermediate dose range (38.1-67.4 mg/m² per cycle), the confirmed objective response rate (ORR) was 23% (6 of 26 patients).²

Within the TNBC subgroup, the confirmed ORR was likewise 23% (3 of 13 patients), and all patients in this cohort had previously received at least 1 topoisomerase I inhibitor antibody-drug conjugate. In evaluable patients with high B7-H4 expression treated at doses of 76.2 mg/m² or greater per cycle, the confirmed ORR was 22% (2 of 9 patients), while 78% (7 of 9 patients) experienced at least a 30% reduction in target lesion size.²

Among the 8 patients achieving confirmed responses at doses of at least 38.1 mg/m², 5 patients experienced greater than 60% reductions in target lesions, including 1 complete response. Additionally, all 4 patients with high B7-H4 expression treated at the initial expansion dose of 67.4 mg/m² administered every 4 weeks achieved tumor shrinkage and remained on therapy for at least 16 weeks at the time of data cutoff.

Patient Characteristics in Phase 1 Trial of Emi-Le

As of the December 13, 2024, data cutoff, 130 patients had received treatment. Across tumor cohorts, the median patient age was 55 years, and patients had undergone a median of 4.5 prior lines of therapy (range, 0-15). B7-H4 status was successfully assessed in 103 patients, of whom 44% were categorized as having high B7-H4 TPS.

Safety of Emi-Le in Phase 1 Trial

Emi-le demonstrated an overall manageable safety and tolerability profile. The most frequently reported treatment-related adverse events (TRAEs) included transient increases in aspartate aminotransferase (AST; 38%; grade 3, 14%), proteinuria (31%; 9%), nausea (29%;1%), and fatigue (28%; 0%). AST elevation and proteinuria were the only grade 3 TRAEs occurring in at least 5% of patients.²

No grade 4 or grade 5 TRAEs were observed, and there were no dose-limiting treatment-related events involving neutropenia, neuropathy, ocular toxicity, interstitial lung disease, or thrombocytopenia. Treatment discontinuation due to TRAEs occurred in 2.3% of patients.

Looking Ahead

"At Servier, we are committed to pursuing first‑in‑class medicines for rare diseases in oncology. This breakthrough therapy designation for Emi‑Le will help accelerate development and may provide an important new treatment option for patients with few effective choices today," Peter Adamson, Global Head, oncology clinical development, Servier, stated in a news release.¹

References

1. Emiltatug ledadotin (Emi-Le) granted breakthrough therapy designation by the U.S. FDA for adenoid cystic carcinoma (ACC). News release. Servier. May 12, 2026. Accessed May 12, 2026. https://servier.mediaroom.com/2026-05-12-Emiltatug-Ledadotin-Emi-Le-Granted-Breakthrough-Therapy-Designation-by-the-U-S-FDA-for-Adenoid-Cystic-Carcinoma-ACC

2. 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