Dr Hanna on the Safety and Efficacy of Emi-Le in Aggressive ACC

“Emi-Le looks like it could be an exciting new therapy for patients with aggressive ACC.”

Glenn J. Hanna, MD, director of the Center for Cancer Therapeutic Innovation (Early Drug Development Program), director of the Center for Salivary and Rare Head and Neck Cancers, and a physician at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, discussed key findings from an interim analysis of a phase 1 trial (NCT05377996) investigating the novel B7-H4–directed antibody-drug conjugate (ADC) emiltatug ledadotin (Emi-Le; XMT-1660) in patients with aggressive adenoid cystic carcinoma (ACC).

Hanna detailed the protocol of administering the drug as a monthly intravenous infusion to evaluate its safety, tolerability, and overall efficacy within this patient population during the phase 1 trial. He emphasized the unique safety profile of Emi-Le, noting that it differs significantly from other ADCs in its class. For example, although many auristatin-based treatments for various cancers are frequently associated with toxicities such as eye issues, lung inflammation, and significant cell count issues or cytopenias, these traditional adverse effects (AEs) were not observed at high rates in the patients with aggressive ACC treated with Emi-Le in the current phase 1 trial, according to Hanna. Instead, he identified proteinuria as a unique but manageable toxicity associated with the agent. He also highlighted that most patients do not require treatment cessation due to this AE, as it can be effectively addressed and co-managed through the use of kidney-supported medications.

Furthermore, Hanna outlined robust antitumor activity observed during the trial. For a patient population characterized by a high unmet medical need, the confirmed response rates are encouraging, he said, stressing that these responses are durable, enabling patients to continue to receive the treatment regimen over long durations without significant safety concerns. Data showed that in evaluable patients with ACC treated across all doses (n = 45), the confirmed overall response rate (cORR) and ongoing unconfirmed response rate (uPR) was 35.6% (95% CI, 21.9%-51.2%), and the median duration of response was 7.4 months (95% CI, 3.1-not reached). Post hoc data showed that for patients with aggressive ACC (n = 32), the cORR/uPR and median DOR were 46.9% (95% CI, 29.1%-65.3%) and 6.4 months (95% CI, 3.1-9.5), respectively.

Regarding survival outcomes, Hanna noted that although it is currently premature to provide definitive overall survival data, there has been a dramatic improvement in progression-free survival with Emi-Le compared with historical data. Hanna concluded that Emi-Le represents an exciting new therapy for aggressive ACC, a sentiment reinforced by the granting of breakthrough therapy designation to the agent for this indication by the FDA in May 2026.