Published April 14, 2022 | Version 1
Journal article Open

Phase I/II multicenter trial of a novel therapeutic cancer vaccine, HepaVac-101, for hepatocellular carcinoma.

Authors/Creators

  • 1. University Hospital Tübingen
  • 2. IRCCS Ospedale Sacro Cuore Don Calabria
  • 3. Istituto Nazionale Tumori - IRCCS "Pascale"
  • 4. Immatics Biotechnologies GmbH
  • 5. University of Birmingham
  • 6. Clinica Universidad de Navarra
  • 7. Antwerp Univ.
  • 8. Université de Nantes
  • 9. CureVac AG
  • 10. University of Tübingen
  • 11. University of Insubria
  • 12. AORN Santobono-Pausilipon

Description

Immunotherapy for hepatocellular carcinoma (HCC) shows considerable promise in improving clinical outcomes. HepaVac-101 represents a single-arm, first-in-man Phase I/II multicenter cancer vaccine trial for HCC (NCT03203005). It combines multi-peptide antigens (IMA970A) with the TLR7/8/RIG I agonist CV8102. IMA970A includes 5 HLA-A*24 and 7 HLA-A*02 as well as 4 HLA-DR restricted peptides selected after mass spectrometric identification in human HCC tissues or cell lines. CV8102 is an RNA-based immunostimulator inducing a balanced Th1/Th2 immune response. 82 patients with very early to intermediate stage HCCs were enrolled and screened for suitable HLA haplotypes and 22 put on study treatment. This consisted in a single infusion of low-dose cyclophosphamide followed by 9 intradermal coadministrations of IMA970A and CV8102. Only patients with no disease relapse after standard of care treatments were vaccinated. The primary endpoints of the HepaVac-101 clinical trial were safety, tolerability and antigen-specific T-cell responses. Secondary or exploratory endpoints included additional immunological parameters and survival endpoints. Results: The vaccination showed a good safety profile. Transient mild-to-moderate injection-site reactions were the most frequent IMA970A/CV8102-related side effects. Immune responses against ≥1 vaccinated HLA class I tumor-associated peptide (TAA) and ≥1 vaccinated HLA class II TAA were respectively induced in 37% and 53% of the vaccinees. Conclusion: Immunotherapy may provide a great improvement in treatment options for HCC. HepaVac-101 is a first-in-man clinical vaccine trial with multiple novel HLA class I- and class II-restricted TAAs against HCC. The results are initial evidence for the safety and immunogenicity of the vaccine. Further clinical evaluations are warranted.

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Additional details

Related works

Is published in
Journal article: 10.1158/1078-0432.CCR-21-4424 (DOI)

Funding

European Commission
HEPAVAC - Cancer Vaccine development for Hepatocellular Carcinoma 602893