Emiltatug ledadotin (Emi-Le): A B7-H4-directed dolasynthen antibody-drug conjugate (ADC) being investigated in phase 1 dose expansion in patients with triple negative breast cancer who received at least one prior topoisomarase-1 inhibitor ADC
Recommended Citation
Han HS, Kalinsky K, Abuhadra N, Giordano A, Starks D, Wulf GM, McAndrew NP, O'Shaughnessy J, Spira AI, Chan N, Kelley K, Parajuli R, Weise AM, Chaudhry A, Wang JS, Richardson DL, Roque DR, Meric-Bernstam F, Rogalski C, Hamilton EP. Emiltatug ledadotin (Emi-Le): A B7-H4-directed dolasynthen antibody-drug conjugate (ADC) being investigated in phase 1 dose expansion in patients with triple negative breast cancer who received at least one prior topoisomarase-1 inhibitor ADC. 2025; (16_suppl):Tps1141.
Document Type
Conference Proceeding
Publication Date
5-28-2025
Abstract
Breast cancer is the leading cause of cancer death for women worldwide, with triple-negative breast cancer (TNBC) considered one of the more aggressive breast cancers, accounting for ∼15% of all cases. Unfortunately, there remains an unmet medical need for effective and well-tolerated treatments for advanced/metastatic TNBC; in heavily pretreated patients, standard-of-care single-agent chemotherapy has limited efficacy, with response rates of ∼5%, PFS ∼7 weeks. Emiltatug ledadotin (Emi-Le; XMT-1660) is a B7-H4-directed Dolasynthen ADC designed with a precise, target-optimized drug-to-antibody ratio (DAR 6) and a proprietary auristatin F-HPA microtubule inhibitor payload with controlled bystander effect. The FDA has granted Emi-Le two Fast Track designations for the treatment of adult patients with breast cancer, including patients with TNBC who have previously been treated with topoisomerase-1 inhibitor (topo-1) ADCs. Initial dose escalation clinical data from the ongoing Phase 1 trial at doses ranging from 38.1-67.4 mg/m2 per cycle demonstrated a 23% confirmed response rate in patients with B7-H4 high TNBC who were heavily pretreated all of whom received at least one prior topo-1 ADC. Methods: Based on encouraging clinical activity and tolerability data in the initial dose escalation data, the expansion portion (EXP) of the Phase 1 trial has been initiated and is actively enrolling patients. EXP has a Simon 2-stage design and will evaluate two doses in patients with advanced/metastatic TNBC who have received 1-4 prior lines of systemic therapy, including at least one topo-1 ADC. Patients will be evaluated for B7- H4 expression prospectively by IHC and will be stratified into B7-H4 TPS high and B7-H4 TPS low cohorts. The first EXP dose is 67.4 mg/m2 Q4W. Dose exploration is ongoing to identify a potential second higher EXP dose. The protocol includes the option for multiple additional indications, including HR+/HER2- breast cancer, endometrial cancer, ovarian cancer, and ACC-1.
Issue
16_suppl
First Page
Tps1141
