FusionVAC22_01: A phase I clinical trial evaluating a DNAJB1-PRKACA fusion transcript-based peptide vaccine combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion

The DNAJB1-PRKACA fusion transcript was identified as the oncogenic driver of tumor pathogenesis in fibrolamellar hepatocellular carcinoma (FL-HCC) as well as in other tumor entities, comprising oncocytic neoplasms of pancreas and bile duct, thus representing a broad target for novel treatment in multiple cancer entities. In preclinical work, we showed that the DNAJB1-PRKACA fusion protein is a source for naturally presented immunogenic neoepitopes and can be actively targeted by T-cell-based immunotherapy (Bauer et al. Nat. Commun., 2022). The DNAJB1-PRKACA fusion-derived neoepitope FusionVAC-22 is a 22mer peptide in silico predicted to bind to 1,290 different HLA class II alleles that contains 13 embedded HLA class I alleles that cover 96.6% and 93.8% of the European and world population with at least one HLA allotype, respectively. Application of FusionVAC-22-based peptide vaccines, adjuvanted with the TLR1/2 agonist XS15 and Montanide ISA51 VG, in two FL-HCC patients was well tolerated without systemic side effects and an induction of a T-cell response six weeks after the second vaccination was observed in both patients. In the first patient specific T cells persisted in peripheral blood and were accompanied by relapse-free survival of the patient until now 27 months post vaccination (Bauer et al. Nat. Commun., 2022). The second patient with metastasized disease was treated in combination with an Immune Checkpoint Inhibitor (ICI). Of note, increased side effects at vaccination site as well as immune related events were not observed in this patient. Most importantly, until now the second patient showed stable disease for 8 months after vaccination. Based on these promising data, we established a Phase I open label, multicentric clinical trial (EU-CT Number 2022-502869-17-00) evaluating the immunogenicity along with safety and toxicity, as well as first signs of efficacy of the FusionVAC-22 based peptide vaccine, combined with an ICI (anti-PD-L1), in 20 patients with locally advanced or metastatic FL-HCC or other malignant disease with proven presence of the DNAJB1-PRKACA fusion transcript.

präsentiert in der Sitzung: Immuntherapie in der GI-OnkologieFreitag, 15. September 2023, 15:00–16:30, Saal X01

 

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Publication History

Article published online:
28 August 2023