Frontiers in Oncology (Mar 2024)

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

  • Christopher Hackenbruch,
  • Christopher Hackenbruch,
  • Christopher Hackenbruch,
  • Jens Bauer,
  • Jens Bauer,
  • Jonas S. Heitmann,
  • Jonas S. Heitmann,
  • Jonas S. Heitmann,
  • Yacine Maringer,
  • Yacine Maringer,
  • Annika Nelde,
  • Annika Nelde,
  • Monika Denk,
  • Monika Denk,
  • Lisa Zieschang,
  • Lisa Zieschang,
  • Christine Kammer,
  • Christine Kammer,
  • Birgit Federmann,
  • Birgit Federmann,
  • Birgit Federmann,
  • Susanne Jung,
  • Susanne Jung,
  • Susanne Jung,
  • Peter Martus,
  • Nisar P. Malek,
  • Nisar P. Malek,
  • Nisar P. Malek,
  • Nisar P. Malek,
  • Nisar P. Malek,
  • Konstantin Nikolaou,
  • Konstantin Nikolaou,
  • Konstantin Nikolaou,
  • Helmut R. Salih,
  • Helmut R. Salih,
  • Michael Bitzer,
  • Michael Bitzer,
  • Michael Bitzer,
  • Michael Bitzer,
  • Juliane S. Walz,
  • Juliane S. Walz,
  • Juliane S. Walz,
  • Juliane S. Walz

DOI
https://doi.org/10.3389/fonc.2024.1367450
Journal volume & issue
Vol. 14

Abstract

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The DNAJB1-PRKACA fusion transcript was identified as the oncogenic driver of tumor pathogenesis in fibrolamellar hepatocellular carcinoma (FL-HCC), also known as fibrolamellar carcinoma (FLC), as well as in other tumor entities, thus representing a broad target for novel treatment in multiple cancer entities. FL-HCC is a rare primary liver tumor with a 5-year survival rate of only 45%, which typically affects young patients with no underlying primary liver disease. Surgical resection is the only curative treatment option if no metastases are present at diagnosis. There is no standard of care for systemic therapy. Peptide-based vaccines represent a low side-effect approach relying on specific immune recognition of tumor-associated human leucocyte antigen (HLA) presented peptides. The induction (priming) of tumor-specific T-cell responses against neoepitopes derived from gene fusion transcripts by peptide-vaccination combined with expansion of the immune response and optimization of immune function within the tumor microenvironment achieved by immune-checkpoint-inhibition (ICI) has the potential to improve response rates and durability of responses in malignant diseases. The phase I clinical trial FusionVAC22_01 will enroll patients with FL-HCC or other cancer entities carrying the DNAJB1-PRKACA fusion transcript that are locally advanced or metastatic. Two doses of the DNAJB1-PRKACA fusion-based neoepitope vaccine Fusion-VAC-XS15 will be applied subcutaneously (s.c.) with a 4-week interval in combination with the anti-programmed cell death-ligand 1 (PD-L1) antibody atezolizumab starting at day 15 after the first vaccination. Anti-PD-L1 will be applied every 4 weeks until end of the 54-week treatment phase or until disease progression or other reason for study termination. Thereafter, patients will enter a 6 months follow-up period. The clinical trial reported here was approved by the Ethics Committee II of the University of Heidelberg (Medical faculty of Mannheim) and the Paul-Ehrlich-Institute (P-00540). Clinical trial results will be published in peer-reviewed journals.Trial registration numbersEU CT Number: 2022-502869-17-01 and ClinicalTrials.gov Registry (NCT05937295).

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