Emiltatug ledadotin (Emi-Le)

Adenoid cystic carcinoma (ACC) is a malignancy of the secretory glands that arises most often in the salivary glands and accounts for approximately 1% of head and neck malignancies. Reported incidence is 3 to 4.5 per million, and approximately 1,200 to 1,300 new cases are diagnosed per year in the United States; Servier states that more than 200,000 people have ACC worldwide. No population registry reports the incidence or prevalence of ACC with solid histology or high-grade transformation. Institutional series indicate the size of the aggressive subgroup: the ACC-I molecular subtype accounted for 20 of 54 tumors (37%) in a proteogenomic cohort, solid-type histology was present in 27.5% of cases in one institutional series, and high-grade transformation was identified in 23 of 412 cases (5.6%) in another. Day One Biopharmaceuticals states that up to 40% of patients have the aggressive form.

Survival is shorter in the aggressive subgroup than in ACC overall. In SEER (3,026 head and neck cases), 5-, 10-, and 15-year survival for ACC overall was 90.3%, 79.9%, and 69.2%. In the proteogenomic cohort, median overall survival was 3.44 years for ACC-I and 23.2 years for ACC-II; a 2026 meta-analysis of 247 participants from 5 cohorts reported a pooled hazard ratio for death of 3.88 (95% CI 2.55 to 5.90) for ACC-I versus ACC-II; and in the axitinib plus avelumab phase II trial median overall survival was 11.3 months for ACC-I compared with 36 months for ACC-II. In the original histologic grading series, 15-year survival was 5% for predominantly solid (grade III) tumors compared with 39% for grade I tumors. NOTCH1-mutant tumors, which are enriched for solid histology, had a median overall survival of 30 months compared with 122 months for wild-type tumors. High-grade transformation has been compared directly with non-transformed ACC in one 1:1 matched series of 23 pairs: mortality was 47.8% (11 of 23) versus 8.7% (2 of 23), 3-year mortality was 34.8% (8 of 23) versus 4.3% (1 of 23), median progression-free survival was 18.0 versus 37.0 months, and median survival after distant metastasis was 8.0 versus 16.5 months, although median follow-up was shorter in the transformed group (29.0 versus 39.0 months). Distant metastasis occurred in 78.3% of transformed cases, and in an earlier 9-participant series 5 died within 5 years, with a median overall survival of 12 months. Among solid-type tumors with distant metastases, 17 of 28 (61%) involved multiple organs. Company sources report a median progression-free survival of 2 to 3 months in aggressive ACC; the median overall survival is given as approximately 3 years in the 2026 Form 10-K and the ASCO 2026 abstract and as 2 to 3 years in a 2025 Mersana announcement.

No systemic therapy is approved by the FDA for recurrent or metastatic ACC. In a meta-analysis of 17 studies of VEGFR inhibitors (560 participants), the pooled objective response rate was 6%. In the only randomized comparator trial, 60 participants with recurrent or metastatic ACC progressing within the previous 9 months were allocated to axitinib or observation and 54 were evaluable: the 6-month progression-free survival rate was 73.0% with axitinib and 23.0% with observation, median progression-free survival was 10.8 versus 2.8 months (hazard ratio 0.25, 95% CI 0.14 to 0.48), and the disease control rate was 100.0% versus 51.9%, but the objective response rate was 0.0% in both groups and median overall survival was not reached with axitinib compared with 27.2 months with observation (P = 0.226). In a real-world cohort of 51 participants treated with lenvatinib at 17 Italian sites, the objective response rate was 21.7% among 46 evaluable participants, median progression-free survival was 14.8 months, and median overall survival was 16.1 months. Outcomes of ACC-I were worse than those of ACC-II across pooled systemic treatment categories in a real-world cohort (hazard ratio 3.06), and with axitinib plus avelumab, median progression-free survival was 1.8 months in ACC-I compared with 11.4 months in ACC-II.

Humanistic and economic burden data specific to aggressive ACC were not identified. The only ACC-specific health-related quality of life study (EQ-5D-5L; 161 participants, 563 questionnaires) reported a median EQ-5D value of 0.81 and a mean of 0.79, below the age-matched general population mean of 0.86, with a median visual analogue scale score of 70; a decrease in value from 1 to 0 was associated with an eightfold increase in the risk of death. Quality of life decreased significantly over time in that cohort, and no clinical variable tested, including NOTCH1 status, primary site, sex, age, and pattern of recurrence, predicted the decline; results were not reported by histologic subtype. No ACC-specific cost-of-illness study was identified. The closest United States estimate comes from claims data for oral cavity, oropharyngeal, and salivary gland cancers combined, in which total healthcare spending in the year after diagnosis was $79,151 in the commercially insured population. In a pilot survey in head and neck cancer, high financial toxicity was reported by 44.4% of caregivers and 25.9% of participants with cancer.