Emiltatug Ledadotin Well Tolerated in Triple-Negative Breast Cancer Phase 1b Study

Emiltatug ledadotin (Emi-Le, XMT-1660) showed encouraging clinical activity and appeared to be well tolerated in a group of previously treated patients with triple-negative breast cancer (TNBC), according to a phase 1b clinical trial.

Erika P. Hamilton, MD, Sarah Cannon Cancer Network, Nashville, Tennessee, presented the study findings during a mini-session at the 2025 European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress held in Munich, Germany.

Patients enrolled in the study had high B7-H4 expression, an immune-suppressive plasma membrane protein that is overexpressed in many tumor types, including breast, endometrial, and ovarian cancers. Of the 130 patients who received Emi-Le, an antibody-drug conjugate (ADC) targeting B7-H4, 63 patients had triple-negative breast cancer (TNBC) and had received a median of four prior lines of therapy. Most of them (92%) previously received one or more topoisomerase 1 antibody-drug conjugates.

“Effective treatments for relapsed/refractory TNBC remain an unmet medical need,” Hamilton said. Moreover, the standard-of-care, single-agent chemotherapy, has limited efficacy with response rates of about 5%.

Therefore, the trial investigated safety and tolerability, overall response rate (ORR), disease control rate, and duration of response.

In dose escalation, patients received Emi-Le doses ranging from 7.2 to 115 mg/m². The researchers then evaluated tumors retrospectively using immunohistochemistry for B7-H4 expression, with a preliminary high cutoff set at a tumor proportion score (TPS) of 70 and above.

Results showed a confirmed ORR of 23% in 13 evaluable patients with TNBC. Furthermore, the three confirmed responders experienced a reduction in target lesions of 60% or above. Seven of the 13 patients received 3 to 4 prior lines of therapy, and the ORR in this group was 29%. At data cutoff, the two responders in this group were still receiving treatment.

In addition, the researchers found Emi-Le, which was fast-tracked by the Food and Drug Administration earlier this year, to be well-tolerated among the patient population. The most common treatment-related adverse events (TRAEs) among all 130 patients were transient increases in AST (38%), proteinuria (31%), nausea (29%), and fatigue (28%). Grade 3 transient AST and proteinuria were experienced by 14% and 9% of patients, respectively. One percent of patients experienced grade 3 nausea.

The researchers observed no grade 4/5 treatment-related adverse events and no dose-limiting treatment-related adverse effects, including neutropenia, neuropathy, ocular toxicity, interstitial lung disease, or thrombocytopenia.

Although these results are promising, Emi-Le continues to be investigated as part of an expansion of the phase 1 trial. Patients with advanced/metastatic TNBC who received at least one line of prior therapy will receive 67.4 mg/m² of the ADC, the researchers said.

Reference

Hamilton EP, Chaudhry A, Spira AI, et al. 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. Abstract 298MO. Presented at the 2025 ESMO Breast Cancer Annual Congress, May 14-17, 2025; Munich, Germany.