ACC is a rare salivary gland cancer with heterogeneous clinical behavior. ACC typically presents with locoregional disease and is treated with curative intent surgery and adjuvant radiation, but many patients develop locally R/M disease even years later. Two recognized molecular subtypes exist: ACC 1 (37%), characterized by MYC amplification and NOTCH-activating mutations and a poor prognosis, and ACC 2 (63%), which demonstrates P63 expression and upregulated EGFR and MET and a better prognosis.

The trial enrolled 21 patients, with 17 evaluable for response at the time of submission. The ORR was 6% (1 partial response), while 53% (n = 9) achieved stable disease (SD) and 41% (n = 7) experienced progressive disease (PD). The median duration of SD was 5.4 months. The most common treatment-related adverse events (TRAEs) included acneiform rash (81%), infusion-related reactions (76%), and fatigue (71%). Grade 3 TRAEs were reported in three patients (14%), consisting of acneiform rash, oral mucositis, and elevated alkaline phosphatase; no Grade ≥4 TRAEs occurred. Median progression-free survival (PFS) was 4.8 months, and median overall survival was 10.4 months. No correlation was observed between tumor P63 or MYC expression and clinical benefit (partial response or stable disease).

KOL insights: 

“The clinical benefit rate was 61%, indicating that amivantamab may be a potential treatment in patients who previously failed many different kinds of therapies with limited available options.” – Expert Opinion

Conclusion:

Adenoid Cystic Carcinoma (ACC) is a rare head and neck cancer with no standard systemic treatment. When it metastasizes, options become limited, outcomes are poor, and resistance to existing drugs further complicates treatment. 

In the absence of an established standard of care for R/M ACC, multi-targeted tyrosine kinase inhibitors remain a commonly utilized approach, though their efficacy is limited. In this study, amivantamab did not meet the pre-specified objective response rate threshold; however, clinical benefit was observed in a substantial proportion of patients. The safety profile was manageable, with treatment-related adverse events primarily consisting of dermatologic and infusion-related toxicities, and no Grade ≥4 events reported. Despite modest survival outcomes, the tolerability and disease stabilization seen in over half of patients suggest a potential role for amivantamab in this setting. Notably, the lack of correlation between P63 or MYC expression and clinical benefit underscores the continued need for robust predictive biomarkers to guide therapeutic selection in ACC. There’s a strong need for new therapies — amivantamab may help overcome resistance mechanisms in ACC, offering improved responses with a manageable safety profile.