Abstract 4366: Individualized neoantigen vaccine as adjuvant therapy in high-risk esophageal carcinoma: A study with the largest reported cohort and longest follow-up to date

Abstract Background: For esophageal carcinoma (EC) patients with residual pathological disease (non-pCR) after neoadjuvant chemoimmunotherapy and surgery, effective adjuvant strategies to reduce recurrence are urgently needed. This study evaluates the safety, efficacy, and immunogenicity of iNeo-Vac-P01, a personalized neoantigen peptide vaccine, in this high-risk setting. To our knowledge, this is the largest and longest-following cohort reported to date for a personalized cancer vaccine in postoperative EC. Methods: In this single-arm trial (NCT05307835), eligible stage IIA-IIIB EC patients with non-pCR received the vaccine. Tumor and matched normal tissues underwent whole-exome and RNA sequencing. Somatic mutations were identified, and up to 20 individualized long peptides (15-30 aa) encompassing predicted HLA class I and II neoantigens were designed and synthesized for each patient using a proprietary bioinformatics platform (iNeo®). Patients received subcutaneous injections of iNeo-Vac-P01 (300 μg/peptide) co-administered with GM-CSF (40 μg) on Days 1, 4, 8, 15±3, 22±3, 52±7, and 82±7. Primary endpoints were safety and 1-year recurrence-free survival (RFS). Results: As of November 15, 2025, 26 patients were enrolled, with 23 constituting the efficacy-evaluable population (65.2% were ypT+N+). All patients completed the initial 7-vaccination course. Treatment-related adverse events were primarily Grade 1-2 (fatigue: 39.1%; fever: 30.4%; injection site reactions: 21.7%), with one Grade III acute hypersensitivity event. With a median follow-up of 25.3 months from surgery, the 1-, 2-, and 3-year RFS rates were 91.3%, 85.6%, and 78.5%, respectively. These outcomes compare favorably with the adjuvant nivolumab arm in the CheckMate 577 trial, which reported a 3-year RFS of 43%. The 1-, 2-, and 3-year OS rates were 100%, 95%, and 83.1%, respectively. ELISpot assays confirmed immunogenicity in 100% (23/23) of patients, with 79.5% (233/296) of administered peptides eliciting de novo T-cell responses. TCR sequencing demonstrated durable expansion of neoantigen-specific T-cell clones, detectable during treatment and for six months after the final vaccination. Conclusion: This study, representing the largest and longest-followed cohort in this context, establishes the individualized neoantigen vaccine iNeo-Vac-P01 as a promising adjuvant strategy for high-risk EC. The compelling survival benefit over historical standards, manageable safety profile, and universal immunogenicity support its potential to change the postoperative management paradigm and warrant further randomized trials. Citation Format: Ming Wu, Hong Shen, Fan Mo, Zixiang Wu, Chuanqiang Wu, Youping Wang, Kailai Wang, Shanshan Zhang, Ning Han, Liqian Wu, Wenjin Zhuang, Shuqing Chen. Individualized neoantigen vaccine as adjuvant therapy in high-risk esophageal carcinoma: A study with the largest reported cohort and longest follow-up to date [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 4366.