Multicenter phase 2 trial of amivantamab for recurrent or metastatic adenoid cystic carcinoma

Adenoid cystic carcinoma (ACC), treated locally with surgery and radiation therapy, has high recurrence and distant failure rates. A phase 2 trial at three centers in the USA evaluated the bispecific antibody amivantamab (targeting EGFR and MET) in adult patients with recurrent or metastatic ACC not amenable to curative-intent therapy, who had progression within 6 months of study enrollment. Patients received amivantamab weekly for one months, followed by day 1 and day 15 dosing every 28 days thereafter until progression. Primary endpoint was best overall response rate (ORR) per RECIST 1.1. Among 21 patients enrolled, 18 were efficacy evaluable. Most primary sites were the major/minor salivary glands (n=17) and 13 had metastatic disease. Nine patients had no prior systemic treatment, and 6 had 2 or more lines of prior therapy. With amivantamab, one patient with type 1 ACC and a somatic EGFR variant had a partial response (best ORR 5.6%; 95% CI 0-27.6), 12 patients (66.7%; 43.6-83.9) achieved stable disease, and 5 patients (27.8%; 12.2-51.2) had disease progression, for a clinical benefit rate of 72.2% (48.8-87.8). Three patients (14%) experienced grade 3 treatment-related adverse events (acneiform dermatitis, mucositis, and elevated alkaline phosphatase. The authors conclude that while the primary endpoint of best ORR was not met in this trial, amivantamab was well tolerated, and most patients exhibited disease stabilization. Amivantamab warrants further exploration alone or in combination in ACC.