Amivantamab Shows Promise in Adenoid Cystic Carcinoma and Head and Neck Cancer Trials
Phase 2 trial of amivantamab in recurrent/metastatic adenoid cystic carcinoma achieved 72.2% clinical benefit rate with good tolerability. Combination therapy with pembrolizumab is being evaluated in head and neck squamous cell cancer.
A phase 2 trial of amivantamab in recurrent or metastatic adenoid cystic carcinoma achieved a clinical benefit rate of 72.2%, though the primary endpoint was not met. The single-arm, open-label trial enrolled 21 patients between October 2022 and January 2025 at 3 US academic centers, with 18 patients evaluable for efficacy.
Adenoid cystic carcinoma is a rare salivary gland tumor treated locally with surgery and radiation therapy. Despite high recurrence and distant failure rates, there is no approved systemic therapy for recurrent/metastatic disease. Amivantamab is a dual-target epidermal growth factor receptor (EGFR)–mesenchymal–epithelial transition (MET) bispecific antibody.
The trial enrolled patients aged 18 years and older with confirmed recurrent/metastatic adenoid cystic carcinoma not amenable to curative-intent therapy, who had progression within 6 months of study enrollment. Participants had at least 1 site of measurable disease by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), an Eastern Cooperative Oncology Group performance status of 0 to 1, and adequate organ and marrow function.
The median age was 61 years (range, 36-76 years), and 14 individuals (67%) were male. Most primary sites were the major/minor salivary glands (17 patients [81%]), and 13 (62%) had distant metastatic disease. Nine patients (43%) had no prior systemic treatment. Six patients (29%) had 2 or more lines of prior therapy.
Patients received intravenous amivantamab, 1050 mg if weighing less than 80 kg, or 1400 mg if weighing 80 kg or more, weekly for 1 month, followed by day 1 and 15 dosing every 28 days thereafter until progression.
Of 18 evaluable patients, best overall response rate was 5.6% (95% CI, 0-27.6%), with 1 partial response in a patient with type 1 adenoid cystic carcinoma and a somatic EGFR variant. Twelve patients (66.7% [95% CI, 43.6%-83.9%]) achieved stable disease. Five patients (27.8% [95% CI, 12.2%-51.2%]) experienced disease progression, yielding a clinical benefit rate of 72.2% (95% CI, 48.8%-87.8%).
Common treatment-related adverse events included acneiform dermatitis (18 [86%]), infusion-related reaction (16 [76%]), and fatigue (15 [71%]). Three patients (14%) experienced grade 3 treatment-related adverse events (acneiform dermatitis, mucositis, and elevated alkaline phosphatase). Patients tolerated treatment well.
While the primary end point of best overall response rate was not met in this nonrandomized clinical trial, amivantamab was well tolerated, and most patients exhibited disease stabilization. This represents one of few clinical trials in advanced adenoid cystic carcinoma to evaluate a dual-targeted therapy; amivantamab warrants further exploration alone or in combination in adenoid cystic carcinoma. The trial is registered as ClinicalTrials.gov Identifier NCT05074940.
Separately, amivantamab plus pembrolizumab is being evaluated in previously untreated recurrent/metastatic head and neck squamous cell cancer in the phase 1b/2 OrigAMI-4 study (NCT06385080). Results from this combination therapy study were presented at the 2026 Multidisciplinary Head and Neck Cancers Symposium, which took place February 19-21, 2026, in Palm Desert, California.