Abstract 2833: Amivantamab restores antitumor immunity in non-small cell lung cancer through EGFR/MET expression-dependent mechanisms

Abstract Introduction: Epidermal growth factor receptor (EGFR) mutations are one of the most common oncogenic drivers in non–small cell lung cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated clinical benefits, acquired resistance still limits the long-term efficacy, with activation of MNNG HOS Transforming (MET) signaling serving as a representative bypass mechanism. Recently, amivantamab, a bispecific antibody against EGFR and MET, has shown clinical efficacy. However, its immunological role in human tumors has not been directly investigated. Methods: We analyzed 40 surgically resected fresh NSCLC samples to evaluate EGFR/MET expression and their correlation with immune suppression. Tumor-infiltrating lymphocytes (TILs) were evaluated by flow cytometry and immunohistochemistry. To assess the immunomodulatory effects of amivantamab, tumor digests including viable TILs were cultured ex vivo under conditions with or without amivantamab. Results: EGFR mutations and elevated EGFR protein expression showed a tendency for reduced infiltration of CD8+ T cells and dendritic cells (DCs). Ex vivo exposure to amivantamab enhanced CD8+ T-cell effector functions and DC maturation in TILs, particularly in tumors with high EGFR/MET expression, independent of EGFR mutation status. Conclusion: This study provides the first direct evidence using fresh human NSCLC samples that amivantamab can restore antitumor immunity through CD8+ T-cell activation and DC maturation. Expression levels of EGFR and MET may serve as predictive biomarkers for amivantamab monotherapy as well as for amivantamab-based combination immunotherapies. Citation Format: Takamasa Ishino, Ryo Yoshichika, Fumiaki Mukohara, Ken Suzawa, Shinichi Toyooka, Yosuke Togashi, . Amivantamab restores antitumor immunity in non-small cell lung cancer through EGFR/MET expression-dependent mechanisms abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2833.