298MO Clinical activity of emiltatug ledadotin (Emi-Le), a B7-H4-directed ADC, in patients with TNBC who received at least one prior topoisomerase-1 inhibitor (Topo-1) ADC
Recommended Citation
Hamilton EP, Han H, Abuhadra N, Kalinsky K, McAndrew NP, Spira A, Chan N, Kelley K, Parajuli R, O'Shaughnessy J, Starks D, Wulf G, Weise AM, Chaudhry A, Wang JS, Richardson DL, Meric-Bernstam F, Burger R, Bradshaw C, Giordano A. 298MO Clinical activity of emiltatug ledadotin (Emi-Le), a B7-H4-directed ADC, in patients with TNBC who received at least one prior topoisomerase-1 inhibitor (Topo-1) ADC. 2025; (S4).
Document Type
Conference Proceeding
Publication Date
5-1-2025
Abstract
Background: Effective treatments for relapsed/refractory TNBC remain an unmet medical need. Standard-of-care single-agent chemotherapy has limited efficacy, with response rates of ∼5%, PFS ∼7 weeks. Emi-Le (XMT-1660) is a B7-H4-directed Dolasynthen ADC designed with a proprietary auristatin F-HPA microtubule inhibitor payload with controlled bystander effect. Methods: The Phase I trial is investigating Emi-Le monotherapy in adult pts with select advanced/metastatic solid tumors, including TNBC. In dose escalation, eligible pts received Emi-Le at doses of 7.2-115 mg/m2. Tumors were evaluated retrospectively by IHC for B7-H4 expression with a preliminary high cutoff set at tumor proportion score (TPS) ≥70. Results: As of Dec 13, 2024, 130 pts were dosed with 4.5 median prior lines of therapy. 63 pts had TNBC, with a median of 4 prior lines (range 2-9) and 92% having previously received ≥1 topo-1 ADC. Among all 130 pts, the most common TRAEs were transient AST increase (38%, G3 14%), proteinuria (31%, G3 9%), nausea (29%, G3 1%) and fatigue (28%, G3 0%). The only G3 TRAEs in ≥5% of pts were AST increase and proteinuria. No G4 or 5 TRAEs were reported. No observed dose-limiting treatment-related neutropenia, neuropathy, ocular toxicity, interstitial lung disease or thrombocytopenia. In the 13 evaluable pts with TNBC and high B7-H4 expression dosed at 38.1-67.4 mg/m2 per cycle, prior lines of therapy ranged 3-8, and all had previously received at least one topo-1 ADC. The confirmed ORR in this population was 23% (3/13). All 3 confirmed responders had reduction in target lesions of >60%. Of the 13 pts, 7 had received 3-4 prior lines; among these, the ORR was 29% (2/7). As of data cutoff, both responders were ongoing on treatment for >16 weeks. Conclusions: Based on the initial reported data, Emi-Le appears to have encouraging clinical activity and tolerability in a heavily pretreated TNBC population with high B7-H4 expression who had previously received topo-1 ADCs. Further clinical development of Emi-Le is ongoing in the expansion portion of the Ph1 trial at a dose of 67.4 mg/m2 Q4W in pts with advanced/metastatic TNBC who have received 1-4 prior lines of systemic therapy, including at least one topo-1 ADC. Clinical trial identification: NCT05377996.
Issue
S4
