20 Adenoid Cystic Carcinoma (ACC) Clinical Trials Recruiting Now (May 2026): NOTCH, ADC, B7-H4, Carbon Ion, Salivary

Last updated: May 25, 2026

Current Clinical Trial Landscape

Active research areas in 2026:

NOTCH-targeted therapy — CB-103 (oral NOTCH inhibitor) in combination trials for NOTCH-mutant ACC
Antibody-drug conjugates (ADCs) — multiple targets reaching ACC patients: c-Kit (NN3201), Nectin-4 (enfortumab vedotin), B7-H4 (XMT-1660 + new entrant AZD8205 / puxitatug samrotecan), TROP2, EGFR (becotatug vedotin / MRG003 neoadjuvant)
Carbon ion radiotherapy — three recruiting trials for locally advanced/unresectable ACC (ACC is relatively resistant to standard photon radiation)
Tyrosine kinase inhibitors — lenvatinib, axitinib, and novel multi-kinase inhibitors
Immunotherapy combinations — ivonescimab (PD-1/VEGF bispecific) for salivary gland cancers; VMD-928 ± pembrolizumab for TrkA-driven tumors
Site-specific approaches — intra-arterial epirubicin chemotherapy for sinonasal ACC (new Phase 2 NCT07320508); SBRT for oligometastatic disease
Rare-tumor basket trials — agnostic therapy protocols (NCT06638931) that accept ACC patients

Standard of care: Surgery with or without adjuvant radiation for localized disease. For metastatic ACC, there are no FDA-approved targeted therapies — making clinical trials especially important. Chemotherapy (cisplatin, doxorubicin, cyclophosphamide) has limited efficacy. Lenvatinib is sometimes used off-label based on phase 2 data. Slow growth means some patients are monitored with active surveillance before starting systemic therapy.

Understanding Adenoid Cystic Carcinoma

ACC is a rare cancer (~1,200 new cases/year in the US) that most commonly arises in salivary glands (parotid, submandibular, minor salivary) but can also occur in the breast, skin, cervix, prostate, and trachea. It behaves differently from most cancers:

Slow but relentless growth — ACC often grows slowly over years, but recurrence is common even 10-15 years after initial treatment
Perineural invasion — ACC has a strong tendency to spread along nerves, which can cause pain and makes surgical margins challenging
Late distant metastases — lung metastases are the most common site of spread, sometimes appearing many years after the primary tumor
Histologic subtypes — solid pattern is most aggressive, cribriform is most common, tubular has the best prognosis. Subtype affects trial eligibility for some studies.

Key Biomarkers for Trial Eligibility

Molecular profiling is increasingly important for ACC — several biomarkers determine eligibility for targeted trials:

NOTCH1/2 mutations — present in ~15-20% of ACC, associated with solid subtype and more aggressive behavior. Required for CB-103 trial (NCT05774899). NOTCH-mutant ACC may also respond to gamma-secretase inhibitors.
MYB-NFIB fusion — the hallmark genetic event in ACC (~60-80%), driving the transcriptional program of the tumor. Not yet directly targetable but a diagnostic marker and potential future therapeutic target.
c-Kit (CD117) expression — overexpressed in ~80-90% of ACC. Target for the ADC NN3201 (NCT06805825). Imatinib showed limited single-agent activity historically.
EGFR expression — present in a subset of ACC. Relevant for EGFR-targeting ADCs like MRG003/becotatug vedotin.
TrkA expression — target for VMD-928 trial. NTRK fusions (rare) are druggable with larotrectinib or entrectinib.

Only 20 ACC-specific trials on ClinicalTrials.gov — we search 70+ by including salivary gland, head & neck, and rare-solid-tumor basket trials too.

Find Matching Trials

Recruiting Trials by Treatment Setting

Locally Advanced / Unresectable — Radiation Approaches

ACC is relatively radioresistant to conventional photon radiation. Carbon ion (heavy particle) therapy delivers higher biological effectiveness and may improve local control:

Carbon ion radiotherapy:
- NCT05733910 - Carbon ion with simultaneous integrated boost
- NCT04214366 - Carbon ion only irradiation
- NCT02838602 - Carbon ions vs standard radiotherapy (randomized)
SBRT for oligometastatic disease:
- NCT04883671 - Stereotactic body RT for oligometastatic ACC

Metastatic / Recurrent — Systemic Therapy

The most active area of ACC research. No standard second-line therapy exists, making trials critical:

NOTCH-targeted therapy:
- NCT05774899 - CB-103 (oral NOTCH inhibitor) + lenvatinib or abemaciclib for NOTCH-mutant ACC (Phase 1/2)
Antibody-drug conjugates (ADCs) — multiple targets converging on ACC:
- NCT06805825 - NN3201 (c-Kit ADC) — targets the most commonly expressed protein in ACC (c-Kit positive in ~80-90%)
- NCT06891560 - Enfortumab vedotin (Nectin-4 ADC) in ACC (Phase 2)
- NCT05377996 - XMT-1660 (B7-H4 ADC) in solid tumors including ACC (Phase 1)
- NCT07162480 - Puxitatug Samrotecan (AZD8205, B7-H4 ADC) in advanced, recurrent or metastatic ACC (Phase 2, new B7-H4 ADC entrant May 2026)
- NCT07522879 - Becotatug vedotin (MRG003, EGFR ADC) + epirubicin as neoadjuvant (Phase 2)
Site-specific chemotherapy approaches:
- NCT07320508 - Intra-arterial epirubicin chemotherapy for sinonasal ACC (SNACC, Phase 2, new May 2026)
Tyrosine kinase inhibitors:
- NCT04974866 - TKIs in metastatic ACC
Novel targeted agents:
- NCT06781567 - HG146 in ACC (Phase 2)
- NCT06118086 - REM-422 for recurrent/metastatic/unresectable ACC (Phase 1/2)
- NCT06462183 - RGT-61159 for relapsed/refractory ACC (Phase 1)
Immunotherapy:
- NCT03556228 - VMD-928 ± pembrolizumab (TrkA-overexpressing tumors)
- NCT06805617 - Ivonescimab (PD-1/VEGF bispecific) for advanced, metastatic salivary gland cancers (Phase 2)
Rare-tumor basket trials (ACC-eligible):
- NCT06638931 - Agnostic Therapy in Rare Solid Tumors (basket study including ACC)

Showing selected notable trials. View all 20 recruiting interventional trials on ClinicalTrials.gov. ACC patients may also be eligible for broader salivary gland cancer trials and head and neck cancer trials.

Frequently Asked Questions

How do I find adenoid cystic carcinoma clinical trials I'm eligible for?

Enter your ACC details into ClinTrialFinder — including tumor location, NOTCH mutation status, histologic subtype, and prior treatments. The AI matches you with trials in minutes. ClinTrialFinder also searches broader salivary gland and head-and-neck cancer trials that may include ACC patients. No login required.

What ACC trials are currently recruiting?

There are 20 recruiting interventional trials specifically for adenoid cystic carcinoma in May 2026 (and many more salivary gland and solid tumor basket trials that include ACC). Active studies include NOTCH-targeted therapy (CB-103), antibody-drug conjugates targeting c-Kit (NN3201), Nectin-4 (enfortumab vedotin), B7-H4 (XMT-1660 and AZD8205 / puxitatug samrotecan), TROP2, and EGFR (becotatug vedotin / MRG003), carbon ion radiotherapy, tyrosine kinase inhibitors, ivonescimab (PD-1/VEGF bispecific) for salivary gland cancers, intra-arterial epirubicin chemotherapy for sinonasal ACC, and rare-tumor agnostic basket trials.

Why are there so few ACC clinical trials?

ACC is a rare cancer (~1,200 cases/year in the US), which makes large clinical trials difficult to conduct. However, ACC patients may qualify for broader trials — many "salivary gland cancer," "head and neck cancer," and "advanced solid tumor" trials include ACC. ClinTrialFinder's basket trial discovery automatically finds these broader trials that may be relevant.

Should I get molecular profiling for adenoid cystic carcinoma?

Yes — molecular profiling can identify actionable targets. NOTCH1/2 mutations (~15-20%) qualify for the CB-103 trial (NCT05774899). c-Kit expression (~80-90%) is relevant for the NN3201 ADC trial. B7-H4 expression qualifies for XMT-1660 and AZD8205 (puxitatug samrotecan) ADC trials. Rare NTRK fusions are druggable with FDA-approved therapies (larotrectinib, entrectinib). Comprehensive genomic profiling (e.g., Foundation Medicine, Tempus) is recommended.

Find ACC Trials Matched to Your Situation

Enter your tumor location, NOTCH status, and treatment history to get AI-matched trial results in minutes.