Background: VXM01 consists of an attenuated Salmonella typhi Ty21a carrying a plasmid encoding for VEGFR-2. The bacterium is serving as a vector via the oral route of administration carrying the plasmid into the Peyer’s plaques. The vaccine construct elicits a systemic T-cell response targeting VEGFR-2. This trial was set up to examine safety and tolerability, clinical and immunogenic response to VXM01 after treatment with at least four vaccinations [10⁶ or 10⁷colony-forming units (CFU)] in patients with recurrent glioblastoma who have failed at least radiochemotherapy with temozolomide. Methods: Patients with progressive resctable glioblastoma were subjected to single oral administration of VXM01 each on day 1, 3, 5, and 7. In addition, VXM01 was allowed to be administered in 4-weekly single doses every 4 weeks during the tumor follow-up period after reoperation. Follow-up was done by weekly safety laboratories and physical examinations in the treatment period and 4-weekly thereafter, MRI including perfusion maps (days 15 and 30 and six-weekly thereafter), 12-weekly T-cell immunomonitoring in the peripheral blood, and brain tumor immunohistochemistry. Results: Eight patients have been treated according to the schedule and surgery has been performed in seven of them. Under VXM01 treatment 47 adverse events, mostly unrelated to VXM01, were observed after a median of 7 doses per patient. Four out of eight patients (50%) showed a VEGFR-2 specific T cell response. In four patients there was a relevant increase in cerebral blood volume and apparent diffusion coefficient on post-vaccination MRI. In one patient there was an objective and durable T1 response, whereas three further patients remained stable prior to surgery and thereafter. Evaluation of infiltrating T cells in the tissue from re-operation revealed an increase in CD8+ T-cells in 5 out of 7 patients relative to the primary tumor tissue. Conclusions: VXM01 was safe and produces specific peripheral immune responses as well as enumeration of tumor-infiltrating T-cells in post-vaccine tumor tissue. Post treatment MRI imply vascular normalization and there was one patient with an objective response. As a consequence of this data, an expansion cohort of this trial has been launched. Clinical trial information: NCT02718443