B-105 Discovery to first-in-man studies of a multi-peptide-based hepatocellular carcinoma vaccine - HEPAVAC

Abstract

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. 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 Immatics' 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. 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 (eg, 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.