Summary: indication under development

Emiltatug ledadotin has no approved indication. The FDA Breakthrough Therapy designation covers locally advanced, recurrent or metastatic ACC with solid histology or high-grade transformation. The phase 1 ACC cohort enrolled adults whose disease met a clinical definition of aggressive ACC and/or a molecular definition (activating NOTCH1 to NOTCH4 mutations, c-Myc positivity, or p63-negative or low tumors). EMBLEM-1 requires both a histopathologic criterion (solid or basaloid histology, or high-grade transformation) and a clinical criterion (progression within 3 years or extrapulmonary metastasis), which matches the stricter definition used in the post hoc analysis of 32 evaluable participants presented at ASCO 2026. Positive B7-H4 expression is not listed as an EMBLEM-1 enrollment criterion in the sources identified; tissue is submitted for B7-H4 testing. The same trial also enrolled participants with breast, endometrial, and ovarian cancers, and two dose expansion cohorts enrolled participants with triple-negative breast cancer previously treated with a topoisomerase-1 inhibitor ADC.

Indication named in the Breakthrough Therapy designation

“It has also received Breakthrough Designation from the FDA for the treatment of patients with locally advanced, recurrent or metastatic adenoid cystic carcinoma with solid histology or high-grade transformation.” (opens the source at this quote in a new tab)

Phase 1: eligibility definition of aggressive ACC

“Eligibility criteria for ACC pts required features consistent with aggressive disease that included 1 of the following: 1) clinically aggressive phenotype, defined as < 3 years to recurrence/progression or de novo metastatic disease with atypical metastatic sites and solid tumor morphology, and/or 2) molecular features consistent with poor prognosis (activating NOTCH1–4 mutations or c-Myc positive or p63 negative/low per IHC).” (opens the source at this quote in a new tab)

Post hoc analysis and EMBLEM-1: clinicopathologic definition of aggressive ACC

“For the post hoc analysis, a stricter clinicopathologic definition required both a histopathologic phenotype (solid/basaloid histology or HGT) and at least one clinical risk factor (progression within 3 years or extrapulmonary metastasis).” (opens the source at this quote in a new tab)
“Tissue is submitted for B7-H4 testing and molecular profiling.” (opens the source at this quote in a new tab)

Other tumor types under study

Field	Quoted record
Conditions	“Triple Negative Breast Cancer”, “Breast Cancer”, “Endometrial Cancer”, “Ovarian Cancer”, “Fallopian Tube Cancer”, “Primary Peritoneal Cavity Cancer”, “Adenoid Cystic Carcinoma”

“To that end, we continue to follow patients in our two dose expansion cohorts in patients with triple-negative breast cancer, or TNBC, who have received one to four prior treatment lines in the locally advanced or metastatic setting, including at least one prior topoisomerase-1 inhibitor, or topo-1, ADC.” (opens the source at this quote in a new tab)