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Background The high postoperative recurrence rate and highly heterogeneous tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) make it difficult for conventional therapies to achieve personalized precision intervention, significantly limiting patient survival benefits. This study aims to evaluate the safety, immunogenicity, and anti-tumor efficacy of the personalized neoantigen peptide vaccine iNeo-Vac-P01 as adjuvant therapy for resectable PDAC patients, exploring a precision immunotherapy strategy targeting tumor-specific neoantigens.Methods This open-label, single-arm clinical trial ( NCT04810910), conducted at Zhejiang Provincial People’s Hospital, enrolled PDAC patients who initiated treatment with iNeo-Vac-P01 following completion of standard adjuvant chemotherapy. The vaccine was administered via multiple subcutaneous injections at a dose of 300 μg/peptide on Days 1, 4, 8, 15, 22, 52, and 82 (7 total doses), with optional quarterly booster immunizations thereafter. Prior to each iNeo-Vac-P01 injection, granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously as an adjuvant. The primary endpoints were safety and recurrence-free survival (RFS), while secondary endpoints included overall survival (OS) and immunogenicity.Results From January 2021 to March 2025, 9 patients with PDAC were enrolled, including 66.7% (6/9) in stage IB-II and 11.1% (1/9) in stage IV. All patients received iNeo-Vac-P01 treatment, 88.9% (8/9) completed seven treatment sessions, and 44.4% (4/9) received two additional booster immunizations. With the time of surgery as the baseline, the median follow-up was 35.6 months (ranging from 9.6 to 64.2 months). The median RFS (mRFS) was not reached. The 3-year RFS rate was 83.3%, the 5-year OS rate was 100%, and all patients survived. Most treatment-related adverse events (TRAEs) were Grades 1-2, mainly fatigue (44.4%), fever (44.4%), and injection site reactions (33.3%). All 9 patients (100%) had antigen-specific immune responses post-treatment, and 77 of 98 peptides (78.57%) could induce antigen-specific responses. Notably, two patients exhibited detectable partial antigen-specific responses in peripheral blood prior to vaccination, which intensified after vaccination.Conclusions iNeo-Vac-P01 demonstrates favorable safety and significant survival benefits when sequentially administered after standard adjuvant therapy for patients with resectable PDAC. The personalized neoantigen selection strategy establishes a novel paradigm for immunotherapy in low tumor mutational burden (TMB) tumors, warranting further validation through prospective multicenter phase II clinical trials.Trial Registration Clinical Trial Registration ID: NCT04810910Ethics Approval Ethics approval was obtained from the ethics committee of Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College. The ID of the ethics approval is 2021KY004. All participants gave informed consent 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.