AMIGO: A phase 2 trial of amivantamab in <i>EGFR</i> or <i>MET-</i> amplified gastroesophageal adenocarcinoma (GEA).

Abstract

394 Background: EGFR (~7%) and c-MET (~5%) amplifications are recurrent events in GEA. While EGFR inhibitors were ineffective in an unselected population, retrospective data suggests benefit in amplified tumors. Amivantamab (ami) is a bispecific anti- EGFR and c-MET antibody. We report results of a multi-center investigator-initiated study of ami in patients with previously-treated EGFR and/or MET -amplified GEA (NCT05117931). Methods: Patients (pts) with advanced GEA who have received ≥1 prior treatment lines and have EGFR and/or MET amp tumors by tissue or plasma cell-free DNA (cfDNA) next generation sequencing (NGS) received ami at 1,050 mg IV weekly (or 1,400 mg if body weight ≥80 kg) in 28-day cycles. The primary endpoint is objective response by RECIST 1.1, and H0 is rejected if ≥ 6/25 (24%) patients achieve an objective response. Survival is stratified by EGFR vs MET and detection by enrollment assay (tissue vs plasma NGS), immunohistochemistry (IHC; 2-3+ by EGFR.113 or MET SP44), and fluorescence in situ hybridization (FISH). Results: At the data cut-off of 9/1/2025, 25 pts received ami with median follow up of 12.9 (range: 1.8-39.8) months. Pts received a median of 2 prior treatment lines (range: 1-5). One patient died of COVID19 after their initial ami dose and was inevaluable for response. Nine of 24 evaluable pts (38%) achieved an objective response ( EGFR amp: 5/17; MET amp: 3/5; both: 1/2). Six responses were confirmed, and the median duration of response was 6.4 (range 1.1-9.7) months. Six of 13 (46%) of patients with tissue amp and 5 of 15 (33%) with ctDNA amp achieved an objective response. Disease control was achieved in 17 of 24 (71%) pts. Median progression-free (PFS) and overall survival (OS) were 3.3 (95% CI 2.1-7.7) and 8.8 (95% CI 5.7-NR) months, respectively (Table). Despite a modest mPFS, 8 (32%) pts had PFS ≥ 7 months. At progression, 6 of 9 responders had persistent target lesion response with new escape lesions, including 2 with CNS metastases. Despite treatment discontinuation, one pt remains disease-free off treatment for over 2 years. Additional biomarker data will be presented. Drug-attributed adverse events were seen in 24 of 25 pts, most commonly infusion reaction (36%; grade 3: 4%) and rash (52%; grade 3: 4%). Conclusions: Ami monotherapy was effective in heavily pre-treated pts with GEA, including tumors with both EGFR and MET amps, and the primary endpoint was met. Despite persistent target lesion control, responders developed mixed responses attributable to resistance via EGFR/MET heterogeneity, co-occurring alterations, and CNS metastasis development. EGFR/MET targeting warrants further evaluation in combination with chemotherapy to address heterogeneity, a common barrier to single agent targeted therapy in GEA. Clinical trial information: NCT05117931 . PFS and OS by gene. mPFS (95% CI) months mOS (95% CI) months EGFR amp 3.5 (2.1-11) 11 (5.7-NR) MET amp 3.3 (3.1-NR) 6.5 (3.6-NR) Both amp 1.5 (0.9-NR) 2.2 (0.9-NR)