Personalized neoantigen vaccine as adjuvant therapy in high-risk postoperative esophageal carcinoma.

Abstract

2511 Background: Effective adjuvant strategies for patients with esophageal carcinoma (EC) with residual pathological disease (non-pCR) following neoadjuvant chemoimmunotherapy and radical surgery are urgently needed to reduce the high risk of recurrence. This investigator-initiated, single-arm clinical trial (NCT05307835) evaluated the safety, efficacy, and immunogenicity of iNeo-Vac-P01, a personalized neoantigen peptide vaccine, administered as adjuvant therapy in this high-risk setting. To our knowledge, this study represents the first and largest global cohort of a personalized neoantigen vaccine for postoperative EC, with the longest follow-up duration to date. Methods: Eligible stage IIA-IIIB EC patients with non-pCR were enrolled. For each patient, somatic mutations were identified, and up to 20 individualized long peptides (15-30 amino acids), encompassing predicted HLA-I and II neoantigens, were designed and synthesized using a proprietary bioinformatics platform. The vaccine (300μg per peptide) was administered subcutaneously in conjunction with GM-CSF (40μg) on a multi-dose schedule (Days 1, 4, 8, 15±3, 22±3, 52±7, and 82±7). The primary endpoints were safety and 1-year recurrence-free survival (RFS). Secondary endpoints included RFS, overall survival (OS), and antigen-specific T-cell responses assessed by ELISpot and TCR sequencing. Results: As of November 15, 2025, 26 patients were enrolled, with 23 patients constituting the efficacy-evaluable population. 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. All 23 patients completed the initial 7-vaccination course. With a median follow-up of 25.3 months from surgery, the 1-year, 2-year, and 3-year RFS rates were 91.3%, 85.6%, and 78.5%, respectively. The corresponding 1-year, 2-year, and 3-year OS rates were 100%, 95%, and 83.1%. These survival outcomes compare favorably with historical controls, notably exceeding the 3-year RFS of 43% reported in the landmark CheckMate 577 trial (adjuvant nivolumab). Immunological analyses confirmed robust vaccine-induced immunogenicity. ELISpot assays detected neoantigen-specific T-cell responses in 100% (23/23) of evaluated patients, with 79.5% (233/296) of the administered vaccine peptides eliciting de novo T-cell activation. TCR sequencing further demonstrated the durable expansion of neoantigen-reactive T-cell clones, which were detectable during treatment and persisted for at least six months following the final vaccination. Conclusions: These results demonstrates that adjuvant therapy with a personalized neoantigen peptide vaccine confers a substantial and durable survival benefit in high-risk EC patients following surgery, coupled with a favorable safety profile. Clinical trial information: NCT05307835 .