Abstract CT217: An open-label, Phase I/IIa study of VB10.NEO (DIRECT-01) in combination with checkpoint blockade in patients with locally advanced or metastatic solid tumors including melanoma, NSCLC, renal cell carcinoma, urothelial cancer or SSCHN
Authors: Krauss Jurgen , Krackhardt Angela , Jager Elke , Williams Anja , Wold Hedda , Gerner Lisa , Sekelja Monika , Schjetne Karoline , Fredriksen Agnete B. , Axelsen Mads 
Published: August 2019

Abstract
BACKGROUND: Neoantigens are ideal for developing personalized cancer vaccines as they are tumor specific and not subject to central tolerance. Targeting neoantigens to generate potent tumor-specific T-cell responses has shown both promising preclinical efficacy as well as clinical responses. VB10.NEO is a DNA plasmid vaccine with intrinsic adjuvant effect designed for efficient delivery of personalized neoepitopes and can hold up unique neoepitopes specific for each patient’s tumor. Here we describe VB N-01 (DIRECT-01), an open-label phase I/IIa study, designed to evaluate the safety, immunogenicity and efficacy of administrating personalized VB10.NEO in combination with checkpoint blockade in up to 40 patients with locally advanced or metastatic solid tumors including melanoma, NSCLC, renal cell carcinoma, urothelial cancer or head and neck cancer. The study is open at 3 clinical study sites in Germany (NCT03548467).
METHODS: The primary objectives are to assess the safety/tolerability of VB10.NEO immunotherapy and determine the feasibility of the VB10.NEO vaccine manufacturing. Secondary objectives are to make a preliminary assessment of the efficacy, to assess the immunogenicity of VB10.NEO immunotherapy, and the correlation between immunological response and clinical efficacy. Eligible patients who have not achieved a confirmed complete response by week 12 on checkpoint blockade as respective standard of care (SOC) will be enrolled in the study. A tumor biopsy and blood sample will be collected and used to identify the patient-specific tumor mutations. A personalized VB10.NEO holding up to 20 unique neoantigens will be designed based on Vaccibody’s proprietary neoepitope selection algorithm NeoSelect™. Patients will receive multiple vaccinations of VB10.NEO at pre-specified time points; an induction phase consisting of 3 injections during the first 6 weeks followed by a maintenance phase with vaccinations every 4th week up to one year from first immunization. VB10.NEO will be administered IM using the PharmaJet® Stratis Needle-free Injection System. A 24 month follow up period will follow the treatment phase. Patients will be assessed for safety, including AEs, vital signs, safety laboratory assessments and ECOG status. Tumor response will be assessed according to the iRECIST criteria. The study aims to characterize the cellular immune response against the individual neoepitopes by IFNγ ELISpot or other immune assays. A descriptive analysis of serial biopsies will also be assessed, including analysis of the mutagenic landscape by exome and RNA sequencing, and IHC to study tumor microenvironment. The trial is currently recruiting patients and initial accrual goal was meet.
Citation Format: Jurgen Krauss, Angela Krackhardt, Elke Jager, Anja Williams, Hedda Wold, Lisa Gerner, Monika Sekelja, Karoline Schjetne, Agnete B. Fredriksen, Mads Axelsen. An open-label, Phase I/IIa study of VB10.NEO (DIRECT-01) in combination with checkpoint blockade in patients with locally advanced or metastatic solid tumors including melanoma, NSCLC, renal cell carcinoma, urothelial cancer or SSCHN [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT217.