Dr Ferrarotto on the Investigation of Emi-Le in Aggressive Adenoid Cystic Carcinoma

“[These data are great news for the ACC community, and we hope that this confirmatory study reads out soon, and that we have a therapeutic option for patients with aggressive ACC.”

Renata Ferrarotto, MD, a professor and Director of Head and Neck Oncology Clinical Research in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed the biologic rationale for and interim findings from a phase 1 study (NCT05377996) evaluating emiltatug ledadotin (Emi-Le), a B7-H4–directed antibody-drug conjugate, in patients with aggressive adenoid cystic carcinoma (ACC).

Notably, these findings were presented at the 2026 ASCO Annual Meeting.

Ferrarotto began by contextualizing ACC as a rare cancer arising in the secretory glands, particularly the salivary glands. Approximately 60% to 70% of patients with this disease eventually experience recurrence despite aggressive local therapy, typically with distant metastases, according to Ferrarotto. She emphasized that no standard-of-care or FDA-approved systemic therapy exists for recurrent metastatic ACC, and that current treatment options, such as chemotherapy and VEGFR inhibitors, yield low overall response rates near 10% at the cost of toxicity, representing a major unmet need.

Ferrarotto explained that transcriptomic analysis has divided ACC into 2 subtypes. She also noted that B7-H4, an inhibitory immune checkpoint protein, is highly expressed in aggressive ACC, rendering it a compelling therapeutic target.

Regarding efficacy data from the phase 1 trial, Ferrarotto reported that among 45 evaluable patients with aggressive ACC, Emi-Le—which carries an auristatin microtubule inhibitor payload—produced a 35.6% (95% CI, 21.9%-51.2%) overall response rate (ORR). In a subgroup of 32 patients defined by histology or clinical characteristics, the ORR reached 46.9% (95% CI, 29.1%-65.3%), with a median progression-free survival of 7.8 months (95% CI, 4.7-11.6). Ferrarotto characterized toxicities as predominantly grade 1 or 2 and transient, most commonly reversible alanine aminotransferase and aspartate aminotransferase elevations, as well as proteinuria, all of which could be managed with dose modifications. She concluded that these data supported FDA breakthrough therapy designation and the ongoing confirmatory phase 2 EMBLEM-1 study (NCT05377996).