Amivantamab for recurrent/metastatic adenoid cystic carcinoma: A multicenter, single-arm, phase 2 clinical trial.

Abstract

6101 Background: Adenoid cystic carcinoma (ACC) is a rare salivary gland cancer with heterogenous clinical behavior. ACC typically presents with locoregional disease and is treated with curative intent surgery and adjuvant radiation, but many patients develop locally recurrent/metastatic (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. There is no standard treatment for R/M ACC, but multi-targeted tyrosine kinase inhibitors are a mainstay of treatment despite their limited efficacy. Amivantamab is a bispecific antibody that binds to the extracellular domains of EGFR and MET, causing immune-directed destruction of cancer cells. Since MET expression renders EGFR inhibitors ineffective, we hypothesized that amivantamab would overcome resistance especially in the ACC 2 subtype. This multicenter, single arm, Phase 2 clinical trial (NCT05074940) evaluated the efficacy of amivantamab in patients with R/M ACC supported by Janssen Pharmaceuticals. Methods: Eligible patients were ≥18 years of age with R/M ACC and had progressive disease (PD) within 6 months of enrollment, ECOG ≤1, with adequate organ and marrow function. Patients received amivantamab 1050 mg or 1400 mg (≥80kg) IV weekly for 4 weeks then Q2 weeks until PD or unacceptable toxicity. The primary end point was overall response rate (ORR) assessed by RECIST 1.1. Among 18 treated patients the lower limit of a one-sided 90% exact binomial CI would be >14% if ≥5 patients respond. Adverse events (AEs) were assessed by CTCAE v5. Secondary end points included progression- free survival (PFS) and overall survival (OS). Key exploratory end points were P63 and MYC expression. Results: We enrolled 21 patients with 17 evaluable for response at time of submission. Most were male (14, 67%) non-Hispanic (20, 95%), and White (19, 90%) with a median age of 61 (range, 36-76) years. The majority received prior treatment. The best ORR was 6% (1 partial response), while 9 (53%) had stable disease (SD) and 7 (41%) PD. Median duration of SD was 5.4 months. The most common treatment-related AEs (TRAEs) were acneiform rash (17, 81%), infusion related reaction (16, 76%), and fatigue (15,71%). Grade 3 TRAEs occurred in 3 patients (14%) including acneiform rash, oral mucositis, and elevated alkaline phosphatase with no Grade ≥4 TRAEs. Median PFS and OS were 4.8 (95% CI, 1.84-7.64) and 10.4 months (95% CI, 5.48-NR), respectively. There was no correlation between tumor P63 or MYC levels and clinical benefit (PR+SD). Conclusions: While amivantamab did not achieve the target ORR, the safety profile was manageable and clinical benefit was observed in 59% of patients. Clinical trial information: NCT05074940 .