Current research has entered into an unprecedented territory of analytical possibilities represented by so called “omics” technologies, allowing the examination of patients and their individual diseases on a previously unimaginable level. This development represents a serious challenge considering established trial designs and research conduct, particularly in early phase clinical trials, since novel theranostics (biomarker based allocation therapies) in principle would allow for patient selection far beyond traditional stratification approaches; further, many different therapeutic combinatorial therapies cannot be easily evaluated in a traditional way within a reasonable timeframe. The summit of this paradigm is biomarker-based selection and manufacturing of a previously undefined drug product directly adapted to patient- and disease-specific features. In our view, such an approach is ideally suited for cancer immunotherapy, since both malignancies and the human immune system require a high level of individuality. Hence, defining naturally presented HLA-Ligands specific for individual malignancies and manufacturing respective T cell targets according to current Good Manufacturing Practice (GMP) standards formulated as a multi-peptide vaccine in a clinical trial is a completely new state of the art approach. On this background, we designed a pilot clinical trial and implemented the required environment, addressing patients with particularly high unmet medical need and exceedingly high relapse rates in an adjuvant setting. The trial follows a platform design including different disease entities, encompassing non-small cell lung cancer (NSCLC), advanced colorectal cancer (CRC), triple negative breast cancer, cholangiocarcinoma, hepatocellular carcinoma (HCC) and high-risk soft tissue sarcoma. Target selection follows a five-pronged approach and is based on analyzing patient autologous tumor material on different omics levels, including the whole exome and transcriptome as well as the HLA-ligandome (comprehensive analysis of the naturally presented HLA ligands on tumor (and benign) tissue by tandem mass spectrometry) to select ideal immunological targets. Further, this trial will endorse a three tier escalation protocol featuring an individual multi-peptide vaccine with Montanide ISA 51 VG and topical imiquimod in a first step, combined with the novel lipopeptide adjuvant XS-15 (TLR7 ligand) and finally introducing a checkpoint inhibitor as a third tier. This pilot trial will primarily focus on endpoints safety and feasibility but endorse various secondary objectives including detailed immunomonitoring of induced vaccine responses and other immune markers. The HCC trial part is supported by the European Commission's 7th Framework Program (www.hepavac.eu).

Citation Format: Sebastian Haen, Markus W. Löffler, Oliver Kohlbacher, Sven Nahnsen, Christopher Mohr, Monika Stieglbaueren, Patricia Hrstic, Luigi Buonaguro, Peter Martus, Maik Häntschel, Cécile Gouttefangeas, Stefan Beckert, Alfred Königsrainer, Stefan Stevanovic, Lothar Kanz, Hans-Georg Rammensee. Phase I trial to evaluate the feasibility and safety of an individualized peptide vaccine of unmodified cancer antigens: PepIVAC-01 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT057.