Abstract
IMPORTANCE: Adenoid cystic carcinoma (ACC) 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. OBJECTIVE: To evaluate amivantamab, a dual-target epidermal growth factor receptor (EGFR)-mesenchymal-epithelial transition (MET) bispecific antibody, as a novel treatment in patients with advanced ACC. DESIGN, SETTING, AND PARTICIPANTS: Between October 2022 and January 2025, this single-arm, open-label, phase 2 nonrandomized clinical trial enrolled patients with recurrent/metastatic ACC at 3 US academic centers. Patients received amivantamab until disease progression or unacceptable toxic effects. Participants were aged 18 years and older with confirmed recurrent/metastatic ACC 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. INTERVENTION: 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. MAIN OUTCOMES: Primary end point was best overall response rate (ORR) per RECIST 1.1. RESULTS: Twenty-one patients enrolled; 18 were efficacy evaluable. 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. Of 18 evaluable patients, best ORR was 5.6% (95% CI, 0-27.6%), with 1 partial response (in a patient with type 1 ACC 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 (TRAEs) included acneiform dermatitis (18 [86%]), infusion-related reaction (16 [76%]), and fatigue (15 [71%]); 3 patients (14%) experienced grade 3 TRAEs (acneiform dermatitis, mucositis, and elevated alkaline phosphatase). CONCLUSIONS: While the primary end point of best ORR was not met in this nonrandomized clinical trial, amivantamab was well tolerated, and most patients exhibited disease stabilization. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05074940.