{
  "abstract": "Background Once failed in standard therapies, patients with advanced digestive system malignancies (e.g., pancreatic and biliary tract cancers) usually face a dismal prognosis and urgently require effective salvage treatments. iNeo-Vac-R01, a novel personalized neoantigen-based mRNA cancer vaccine, was developed and evaluated in this study for its safety, feasibility, and preliminary efficacy in this patient population.Methods This open-label single-arm clinical trial was conducted utilizing a 3 + 3 dose-escalation design (i.e., 50 μg, 100 μg, and 150 μg). The vaccine was administered subcutaneously every 21 days, with a maximum of nine doses. The eligibility criteria included patients with histopathologically confirmed advanced digestive system tumors who had failed standard therapy. The primary endpoints were safety and feasibility, while secondary endpoints included progression-free survival (PFS), overall survival (OS), and immunogenicity.Results From August 2023 to March 2025, a total of 9 patients were enrolled (5 with pancreatic cancer, 2 with cholangiocarcinoma, 1 with esophageal cancer, and 1 with gastric cancer). The median age was ≥65 years (77.8% of patients). All patients had failed second-line or later therapy (44.4% had received >3 lines of prior therapy). As of March 31, 2025, 55% (5/9) of patients had completed 9 treatment cycles, with a median follow-up time of 9.3 months (ranging from 2.3 to 12.8 months). No dose-limiting toxicities (DLTs) or treatment-related adverse events (TRAEs) of Grade 3 or higher were observed in any of the three dose cohorts. The observed TRAEs were mainly Grades 1-2, such as injection site reactions (33.3%-100%), fever (25%-33%), and fatigue (33.3%), which resolved spontaneously or after symptomatic treatment. The median PFS was 3.6 months (95% CI: 3.0-4.2), and the median OS was 9.3 months (95% CI: 3.2-15.4). The 12-month survival rate was 44.4%. Both mPFS and mOS exceeded historical data for second- or third-line standard therapies in advanced pancreatic, biliary, esophageal, or gastric cancers. All nine patients (100%) exhibited neoantigen-specific T cell responses post-treatment, with 35.6% (53/149) of the applied neoantigens inducing antigen-specific T cell responses. The results of ELISpot assays showed that a single neoantigen peptide could induce up to 374 spots per 2×10 5 PBMCs.Conclusions iNeo-Vac-R01 showed good safety and feasibility for treating advanced digestive system tumors in this late-line setting. Its preliminary efficacy was non-inferior to historical controls, and it effectively elicited neoantigen-specific T cell immune responses. This vaccine offers a potential new immunotherapeutic option for patients who have exhausted standard treatments, warranting further validation in larger cohorts.Trial Registration Clinical Trial Registration: NCT06019702Ethics Approval Ethics approval was obtained from the ethics committees of Sir Run Run Shaw Hospital, affiliated with Zhejiang University School of Medicine. The ID of the approval is 2023-0465. Written informed consent was obtained from the patients before taking part.Consent Written informed consent was obtained from the patients for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the editor of this journal.",
  "authors": [
    {
      "affiliations": [
        "Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Yifan Wang"
    },
    {
      "affiliations": [
        "Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou, Zhejiang, China",
        "Hangzhou AI-Force Therapeutics Co., Ltd., Hangzhou, Zhejiang, China"
      ],
      "name": "Fan Mo"
    },
    {
      "affiliations": [
        "Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Yinghua Xu"
    },
    {
      "affiliations": [
        "Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Nan Liu"
    },
    {
      "affiliations": [
        "Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou, Zhejiang, China"
      ],
      "name": "Shanshan Zhang"
    },
    {
      "affiliations": [
        "Hangzhou AI-Nano Therapeutics Co., Ltd, Hangzhou, Zhejiang, China"
      ],
      "name": "Ning Han"
    },
    {
      "affiliations": [
        "Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou, Zhejiang, China"
      ],
      "name": "Xiangjian Chen"
    },
    {
      "affiliations": [
        "Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou, Zhejiang, China"
      ],
      "name": "Shuqing Chen"
    },
    {
      "affiliations": [
        "Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Xiujun Cai"
    }
  ],
  "title": "491 A single-arm clinical trial of iNeo-Vac-R01 for advanced digestive system tumors refractory to standard therapy",
  "uid": "57a8ce97-c6de-5f8b-9592-ace42a5dd547"
}