Abstract A043: Discovery to first-in-man studies of a multi-peptide-based hepatocellular carcinoma vaccine adjuvanted with CV8102 (RNAdjuvant®): HEPAVAC

Hepatocellular (HCC)/normal adjacent tissue matched samples have been collected for HLA immunopeptidome analysis. 17 HCC samples from HLA-A*02 + patients and 15 samples from HLA-A*24 + patients have been analysed by mass spectrometry (LC-MS/MS). RNA-expression profiles have been established for 12 HCC samples. HLA-presentation/expression of peptides on primary HCC samples (as well as mRNA expression) were compared to normal tissue samples from relevant organs (including heart, brain, lung, kidney, liver, nerve, skin etc.) present in the Immatics9 database. A total of 16 peptides have been selected and confirmed for immunogenicity for the HepaVac vaccine and are currently synthesized according to GMP standard. Of these, 7 are restricted to HLA-A*02; 5 to HLA-A*24 and 4 to HLA class II. Formulation development studies have been undertaken leading to a suitable and stable pharmaceutical form. An analytical method was developed which allows the characterization of each individual peptide within the HepaVac vaccine (IMA970A). At present, preclinical studies assessing the combination of the immunological RNA-based adjuvant (RNAdjuvant®) with the peptide-based HepaVac vaccine IMA970 are conducted. A single-arm, first-in-man trial entitled HepaVac-101 is designed to investigate in patients with very early, early and intermediate stage of HCC the off-the-shelf multi-peptide-based HCC vaccine (IMA970) plus the CV8102 adjuvant (RNAdjuvant®) following a single pre-vaccination infusion of low-dose cyclophosphamide acting as an immunomodulator. The study drugs are applied without concomitant anti-tumor therapy with the intention to reduce risk of tumor recurrence/progression in patients who have received all indicated standard treatments. The primary endpoints are safety, tolerability, and immunogenicity. Secondary/exploratory endpoints are additional immunological parameters in blood (e.g. regulatory T-cells, myeloid-derived suppressor cells, impact of the standard therapy on the natural immune response), infiltrating T-lymphocytes in tumor tissue, biomarkers in blood and tissue, disease-free survival/progression-free survival and overall survival. Once safety of this vaccination approach has been determined in the first 10-20 patients the addition of a checkpoint inhibitor will be considered. Suitable patients enrolled in Tuebingen are invited to participate in a trial extension investigating an actively personalized vaccine (APVAC) plus CV8102. The HepaVac project started in September 2013 and is supported by the European Commission9s 7th Framework Program under the Grant Agreement Nr. 602893 (www.hepavac.eu). The clinical trial HepaVac-101 will be conduct in 6 centers located in 5 European countries, i.e. Italy (Naples and Varese), Germany (Tubingen), UK (Birmingham), Spain (Pamplona) and Belgium (Antwerpen). Citation Format: Andrea Mayer-Mokler, Roberto Accolla, Yuk T. Ma, Regina Heidenreich, Francesco Izzo, Alfred Koenigsrainer, Markus Loeffler, Christian Flohr, Phillip Mueller, Sarah Kutscher, Hans-Georg Rammensee, Bruno Sangro, Sven Francque, Danila Valmori, Toni Weinschenk, Carsten Reinhardt, Ulrike Gnad-Vogt, Harpreet Singh, Luigi Buonaguro. Discovery to first-in-man studies of a multi-peptide-based hepatocellular carcinoma vaccine adjuvanted with CV8102 (RNAdjuvant®): HEPAVAC [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A043.