Abstract 852: A novel EGFR neoantigen-specific mRNA cancer vaccine demonstrates immunogenicity and anti-tumor efficacy in human
Authors: Wenhua Liang, Bo Cheng, Jingshu Ma, Yan Wu, Liang Du, Peng Gao, Zhenxing Yang, Wenjie Song, Bo Ying, Jianxing He
Journal: Cancer Research (2025)

Abstract Activating mutations in the epidermal growth factor receptor (EGFR) gene occur in 10-20% of Caucasian and 40% of Asian non-small cell lung cancer (NSCLC) patients. Predominant ones among these are in-frame deletions in exon 19 and the L858R point mutation in exon 21, which constitute 85-90% of all tyrosine kinase domain mutations. Although targeting these mutations has led to the early success of tyrosine kinase inhibitors, all patients eventually will develop resistance to treatment. Immunotherapy has been extensively explored in NSCLC patients in the recent years, but treatment outcome is still unsatisfying. As peptide-based neoantigens targeting EGFR mutations have demonstrated the potential of eliciting robust T cell responses against cancer cells, the combination of immune checkpoint inhibitor (ICI) and cancer vaccine has become a promising approach in fighting NSCLC. Here, we reported an mRNA-based cancer vaccine targeting mutated EGFR led to great anti-tumor efficacy in patients either in monotherapy or in combination of ICI. ABO2013 is an mRNA-based cancer vaccine targeting three most common EGFR mutations including exon 19 deletions, L858R, and T790M mutations. Mutation-specific T-cell responses induced by ABO2013 were initially tested using human PBMCs and transgenic mice expressing prevalent human HLA-A alleles, then anti-tumor efficacy was assessed in EGFR mutation-bearing mouse models. Intramuscular injection of ABO2013 elicited a robust adaptive T-cell response specifically targeting the three encoded EGFR mutations. The activated T cells demonstrated potent cytotoxic activity against tumor cells harboring the corresponding mutations, as evidenced by both in vivo and in vitro anti-tumor efficacy assessment. A first-in-human dose-escalation trial was conducted to further evaluate clinical safety and efficacy of ABO2013 in treating NSCLC patients (ChiCTR2300071001). Eligible participants include those carrying EGFR exon 19 deletions and/or L858R and/or T790M mutations. Participants must have also failed of standard of cares. Different doses of ABO2013 monotherapy or in combination with sintilimab 200mg were administered every 3 weeks to evaluate the safety, immunogenicity and antitumor efficacy. A total of 30 patients have been treated with either ABO2013 monotherapy (n=20) or in combination with sintilimab (n=10) by October 29, 2024. No dose-limiting toxicities or grade 3-4 TRAEs have been observed. Notably, robust neoantigen-specific immune responses were detected with patients achieving complete remission or partial response, respectively. ABO2013, as a monotherapy and in combination with sintilimab, has exhibited a favorable safety profile and a robust neoantigen-specific immune response and promising antitumor activity, warranting further investigation in EGFR-mutated NSCLC population. Citation Format: Wenhua Liang, Bo Cheng, Jingshu Ma, Yan Wu, Liang Du, Peng Gao, Zhenxing Yang, Wenjie Song, Bo Ying, Jianxing He. A novel EGFR neoantigen-specific mRNA cancer vaccine demonstrates immunogenicity and anti-tumor efficacy in human [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 852.