FusionVAC22_02, a phase I clinical trial in progress: Adjuvant <i>DNAJB1-PRKACA</i> fusion transcript–based peptide T-cell activator for fibrolamellar hepatocellular carcinoma (FLC) and other tumor entities carrying the oncogenic driver fusion.

TPS4270 Background: The DNAJB1-PRKACA fusion transcript was detected as the oncogenic driver of tumor pathogenesis in fibrolamellar hepatocellular carcinoma (FLC) and other cancers, e.g. oncocytic neoplasms of pancreas and bile duct. We and others have shown that the fusion protein can be targeted by T cell-based immunotherapy: Application of Fusion-VAC-XS15 a peptide-based T cell activator including the TLR1/2 agonist XS15 emulsified in Montanide ISA 51 VG in two FLC patients was well tolerated without systemic side effects and induced long-lasting T-cell response accompanied by disease remission with a progression-free survival of up to 80 months and 60 months in both patients (Bauer et al. Nat. Commun., 2022). Based on these promising data, Fusion-VAC-XS15 combined with Atezolizumab is currently under evaluation in the advanced or metastatic situation since October 2023 (Hackenbruch et al. Front Oncol., 2024; NCT05937295). For localized FLC, surgical resection still represents the only curative treatment option but shows high relapse rates which underscores the high medical need for adjuvant treatment options. We here present the FusionVAC22_02 trial, which evaluates Fusion-VAC-XS15 as an adjuvant therapeutic in FLC patients who have reached complete remission. Methods: FusionVAC22_02 is a Phase I open label, multicentric clinical trial evaluating immunogenicity along with safety, toxicity and first signs of clinical efficacy of Fusion-VAC-XS15 as adjuvant treatment, in 20 patients with FLC or other cancers with proven DNAJB1-PRKACA fusion protein, and lacking adjuvant treatment options. One key eligibility criterion is achievement of complete remission (e.g. due to surgery, radiotherapy, local intervention or systemic treatment) according to RECIST1.1. Of note, a history of liver transplantation or prior immune-mediated side effects (e.g. after treatment with checkpoint-inhibitors) are no exclusion criteria. Fusion-VAC-XS15 is applied twice in a 4-week interval, with an optional booster 56 days after the second application, followed by a 6-month follow-up. Primary objectives include assessment of immunogenicity in terms of peptide-specific T cell responses, as well as evaluation of safety and toxicity. Safety assessment is based on the frequency of adverse events according to CTCAE v5.0. Clinical efficacy is determined by RECIST1.1 assessment on imaging. Recruitment started in July 2025, nine FLC patients from various parts of the world have been included and treated so far, four of which have reached the primary endpoint. Clinical trial information: NCT06789198 .