Abstract LB-094: Hepavac-101 first-in-man clinical trial of a multi-peptide-based vaccine for hepatocellular carcinoma
Authors: Buonaguro Luigi , Mayer Andrea , Loeffler Markus , Missel Sarah , Accolla Roberto , Ma Yuk Ting , Chaumette Tanguy , Heidenreich Regina , Königsrainer Alfred , Ludwig Joerg , Alcoba Diego , Schuster Heiko , Gouttenfangeas Cecile , Forlani Greta , Tagliamonte Maria , Ascierto Paolo A. , Avallone Antonio , Borrelli Marco , Rammensee Hans-Georg , Sangro Bruno , Iñarrairaegui Mercedes , Francque Sven , Vonghia Luisa , Gori Stefania , Weinschenk Tony , Reinhardt Carsten , Gnad-Vogt Ulrike , Singh Harpreet 
Published: September 2020

Abstract
Background and Aims: Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer globally with an extremely variable 5-year survival rate. Immunotherapy strategies for HCC may represent a key therapeutic tool to improve clinical outcome in HCC patients. HepaVac-101 (EudraCT Number: 2015-003389-10; NCT03203005), is a single-arm, first-in-man Phase I/II clinical trial evaluating a therapeutic cancer vaccine in patients affected by HCC. It is a highly innovative, novel approach based on a multi-peptide vaccine (IMA970A) combined with the TLR7/8/RIG I agonist CV8102 as an adjuvant.
Method: The IMA970A off-the-shelf vaccine includes 5 HLA-A*24 and 7 HLA-A*02 as well as 4 HLA-DR restricted peptides identified and selected from native human HCC tumor tissue by applying the XPRESIDENT® discovery platform. CV8102 is a novel ribonucleic acid (RNA) based immunostimulatory agent inducing a balanced Th1/Th2 immune response.HLA-A*02 and/or A*24-positive patients with very early, early and intermediate stage HCCs have been enrolled to be treated with 9 intradermal vaccinations consisting of IMA970A plus CV8102 following a single pre-vaccination infusion of low-dose cyclophosphamide acting as an immunomodulator. Patients have completed standard of care treatments at time of enrolment and received study drugs without concomitant anti-tumor therapy with no evidence of disease reactivation. The primary endpoints of the HepaVac-101 clinical trial are safety, tolerability, and antigen specific T cell response. Secondary/exploratory endpoints are additional immunological parameters in blood, infiltrating T-lymphocytes in tumor tissue, biomarkers in blood and tissue, disease-free survival/progression-free survival and overall survival.
Results: Patients were enrolled in 6 centers located in 5 European countries i.e. Italy (Naples and Negrar/Varese), Germany (Tübingen), UK (Birmingham), Spain (Pamplona) and Belgium (Antwerp). The end of trial (EOT) was reached on last December 20, 2019. 82 HCC patients have been screened for suitable HLA haplotypes, 22 patients were put on study treatment (i.e. received at least the pre-treatment with cyclophosphamide). The vaccination showed a good safety profile with no major SAE nor AESI reported during the protocol. Immunogenicity data are currently evaluated and will be available at time of the meeting.
Conclusion: The HEPAVAC-101 clinical trial is the achievement of the HEPAVAC Consortium supported by the European Commission's 7th framework program with contract No. 602893 (www.hepavac.eu).
Citation Format: Luigi Buonaguro, Andrea Mayer, Markus Loeffler, Sarah Missel, Roberto Accolla, Yuk Ting Ma, Tanguy Chaumette, Regina Heidenreich, Alfred Königsrainer, Joerg Ludwig, Diego Alcoba, Heiko Schuster, Cecile Gouttenfangeas, Greta Forlani, Maria Tagliamonte, Paolo A. Ascierto, Antonio Avallone, Marco Borrelli, Hans-Georg Rammensee, Bruno Sangro, Mercedes Iñarrairaegui, Sven Francque, Luisa Vonghia, Stefania Gori, Tony Weinschenk, Carsten Reinhardt, Ulrike Gnad-Vogt, Harpreet Singh. Hepavac-101 first-in-man clinical trial of a multi-peptide-based vaccine for hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-094.