Detalle Publicación

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

Autores: Loffler, M. W.; Gori, S.; Izzo, F.; Mayer-Mokler, A.; Ascierto, P. A.; Koenigsrainer, A.; Ma, Y. T.; Sangro Gómez-Acebo, Bruno Carlos; Francque, S.; Vonghia, L.; Inno, A.; Avallone, A.; Ludwig, J.; Duarte Alcoba, D.; Flohr, C.; Aslan, K.; Mendrzyk, R.; Schuster, H.; Borrelli, M.; Valmori, D.; Chaumette, T.; Heidenreich, R.; Gouttefangeas, C.; Forlani, G.; Tagliamonte, M.; Fusco, C.; Penta, R.; Iñarrairaegui Bastarrica, Mercedes; Gnad-Vogt, U.; Reinhardt, C.; Weinschenk, T.; Accolla, R. S.; Singh-Jasuja, H.; Rammensee, H. G.; Buonaguro, L. (Autor de correspondencia)
Título de la revista: CLINICAL CANCER RESEARCH
ISSN: 1078-0432
Volumen: 28
Número: 12
Páginas: 2555 - 2566
Fecha de publicación: 2022
Purpose: Immunotherapy for hepatocellular carcinoma (HCC) shows considerable promise in improving clinical outcomes. HepaVac-101 represents a single-arm, first-in-human phase I/II multicenter cancer vaccine trial for HCC (NCT03203005). It combines multipeptide 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. Patients and Methods: A total of 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 nine 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 immunologic 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. Conclusions: Immunotherapy may provide a great improvement in treatment options for HCC. HepaVac-101 is a first-in-human 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.