A pilot study of a personalized cancer vaccine in combination with immune checkpoint inhibitor in advanced pancreatic cancer.

Abstract

e16434 Background: Neoantigens, derived from somatic mutations, have emerged as a compelling therapeutic target. Vaccines targeting these neoantigens are designed to overcome current limitations in cancer therapy by activating tumor-specific T-cell responses. HRXG-K-1939 is a novel lipid nanoparticle (LNP)-encapsulated, mRNA-based personalized cancer vaccine (PCV). This investigator-initiated trial evaluated the safety, efficacy, and immunogenicity of HRXG-K-1939 in combination with immune checkpoint inhibitors (ICI) in patients with heavily pretreated advanced pancreatic cancer. Methods: Patients who had progressed after at least two lines of systemic therapy and had measurable disease (per RECIST v1.1) were enrolled and received up to 9 doses of HRXG-K-1939 (IM) combined with an ICI. Key endpoints were safety, clinical efficacy, immunogenicity assessed by ELISpot. Results: As of January 26, 2026, five eligible patients with advanced pancreatic cancer were enrolled: four had an ECOG performance status of 1, and one had a status of 0. In terms of prior therapies, four patients had received three lines of chemotherapy, and one had received two lines. All of them received at least one dose of PCV [0.14 mg (n = 3) and 0.4 mg (n = 2)] , shown a tolerable safety profile. All TRAEs were CTCAE grade 1-2, mainly including injection site reactions (100%) and fever (100%). No dose limiting toxicity was observed. Among the five patients, three experienced rapid disease progression following vaccination, while one achieved a partial response (PR) and one maintained stable disease (SD) resulting in an objective response rate (ORR) of 20%. Notably, both patients who achieved PR and SD completed the full course of nine vaccine doses. Patient-01, a 63-year-old male (0.14 mg cohort, post-3L treatment) maintained stable disease and remains alive with ongoing survival of 28.0 months since enrollment. Patient-02, a 33-year-old female (0.4 mg cohort, post-2L treatment) had a 31.7% reduction after nine doses vaccination, which enabled curative-intent surgery; she has been disease-free for > 5.4 months with an overall survival > 15 months since enrollment. Of note, immunogenicity analysis in these two patients revealed positive neoantigen-specific T-cell responses (ELISpot), with peptide response rates of 91.7% (11/12) and 100% (20/20). The responses emerged as early as cycle 3 and were sustained through cycle 9. Conclusions: HRXG-K-1939 combination with ICI demonstrated a manageable safety profile, along with encouraging signs of efficacy and immunogenicity in this study. These findings support the further development of personalized neoantigen vaccines in advanced pancreatic cancer. Clinical trial information: ChiCTR2300077339.