Name: Emiltatug ledadotin (Emi-Le) in Adenoid cystic carcinoma with solid histology or high-grade transformation: Investigational therapies in clinical trials
Published: 2026-09-17T22:01:26-04:00

Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Investigational therapies in clinical trials

5 evidence topics · 14 sources

Guideline recommendations for clinical trial participation

“Given the disappointing results of systemic treatments, participation in clinical trials is strongly recommended.” (opens the source at this quote in a new tab)
“In case of activated NOTCH mutation, participation in a NOTCH inhibitor clinical study is recommended, if possible [V, B].” (opens the source at this quote in a new tab)
“In case of R/M disease, consider sequencing (NGS) of the tumour [V, C].” (opens the source at this quote in a new tab)

“ACCs are rare tumors for which there are currently few effective medical treatments. It is therefore recommended to include patients in clinical trials.” (opens the source at this quote in a new tab)

NOTCH inhibitors: AL101 (ACCURACY) and brontictuzumab

Field	Registry record
Official title	“A Phase 2, Open-Label, Multi-center Study of AL101 in Patients With Adenoid Cystic Carcinoma (ACC) Bearing Activating Notch Mutations”
Primary outcome	“Overall Response Rate (ORR)”
Overall status	“Completed”

“in a phase II trial with 82 patients with NOTCH‐mutated recurrent/metastatic ACC, AL101 produced a 69% disease control (PR plus SD) rate, and 12% of patients had a PR” (opens the source at this quote in a new tab)
“Twenty‐nine patients were included, with a predominance of solid histology (86%).” (opens the source at this quote in a new tab)
“BOR revealed partial response in 17% of patients, stable disease in 55%, and progressive disease in 28%. Median response duration was longer for AL101 compared to brontictuzumab (9.9 vs. 1.7 months, p = 0.04). Median PFS with NOTCH inhibitor was 4.2 months (95% CI 2.7–8.6 months).” (opens the source at this quote in a new tab)
“However, limited PFS and progression of nontarget lesions suggest the potential need for combination therapy to address ACC heterogeneity.” (opens the source at this quote in a new tab)

B7-H4-directed antibody-drug conjugates: AZD8205 (puxitatug samrotecan) in ACC-I

Field	Registry record
Brief title	“Phase II Trial of Puxitatug Samrotecan (AZD8205) in Advanced, Recurrent or Metastatic (R/M) Aggressive Adenoid Cystic Carcinoma Subtype I (ACC-I)”
Brief summary	“Phase II open label study designed to evaluate the efficacy and safety of P-Sam in patients with aggressive, solid, NOTCH mutant or p63 low (B7-H4 high) R/M ACC-I patients.”
Eligibility (ACC-I definition)	“Solid histology and clinical course characterized by < 3 years from diagnosis to initial recurrence or progression or de novo metastatic disease with extra-pulmonary metastasis”
Overall status	“Recruiting”

“Two ACC-I/B7-H4-high PDXs obtained 90% complete responses to a single dose of AZD8205, but none were observed with isotype-conjugated payload or in an ACC-II/B7-H4 low PDX.” (opens the source at this quote in a new tab)

Immune checkpoint inhibitors

“For patients who are candidates for systemic therapy, checkpoint inhibitors should not be routinely offered at this time except for patients with selected molecular alteration (high tumor mutational burden [TMB], MSI-H).” (opens the source at this quote in a new tab)

“The primary efficacy endpoint (≥4 objective responses) was met in cohort 2 (5/32, 16%) but not in cohort 1 (2/32, 6%).” (opens the source at this quote in a new tab)
“This study shows that nivo+ipi has limited efficacy in ACC, albeit with infrequent, exceptional responses, and that it could be promising for non-ACC SGCs, particularly salivary duct carcinomas.” (opens the source at this quote in a new tab)

Emerging mechanism-based agents

“New agents targeting oncogenic drivers, such as NOTCH1 mutations and epigenetic regulators like PRMT5, have demonstrated preliminary activity in early-phase clinical trials. Additional strategies, including B7-H4 targeted antibody-drug conjugates, MYB-directed vaccines and degraders, and MDM2 inhibitors for TP53 wild-type tumors, offer strong biological rationale for further development.” (opens the source at this quote in a new tab)