KS05.6.A Oral DNA vaccination targeting VEGFR2 combined with the anti-PD-L1 antibody avelumab in patients with progressive glioblastoma - final results. NCT03750071

Abstract Background Vascular endothelial growth factor receptor (VEGFR)2 overexpression on glioblastoma endothelia serves as a target for VEGFR2 primed T cells using VXM01 DNA vaccine encoding VEGFR2. is delivered in bacterial Ty21a carrier suitable oral administration. A previous phase I/II study 14 patients with progressive showed positive correlation of specific well altered intra-tumoral immunity prolonged overall survival. One partial response was reported alone. The current trial aimed at intensifying the efficacy signal and testing co-administration checkpoint inhibitor. Material Methods multicentre, open-label (EudraCT 2017 003076 31) included 28 (25 non-resectable, 3 resectable) after standard chemoradiotherapy. administered day 1, 3, 5, 7 followed by boostings q4w. Avelumab (800 mg) given intravenously q2w. Treatment continued up to week 96 2-year observation period. Endpoints safety tolerability, objective rate (ORR), clinical immune-response assessment Neurooncology criteria (iRANO), immunological assays like ELISpot, FACS, tumor immune biomarkers. Results 106 or 107 CFU plus avelumab completed all patients. No treatment-related toxicities were observed. Three responses (according iRANO) reductions 58, 81 95% baseline, respectively, non-resectable (Objective (ORR) 12% (3/25)). Two these progression-free > 12 months. Best additional SD including one patient 6 In resected patient, shrinkage 30% each observed initial treatment before resection subsequent incomplete resection, associated survival 18 months, accompanied an increase intratumoral CD8+ T-cells. Conclusion combination safe produced detectable peripheral VEGFR-2-specific responses. non-resected had response, three more experienced best stable disease. For future studies enrichment strategy based biomarkers might be envisaged.