ATIM-35. VXM01 PHASE I STUDY IN PATIENTS WITH PROGRESSIVE GLIOBLASTOMA – FINAL RESULTS
| Autor: | Andreas von Deimling, Andreas Unterberg, Heinz Lubenau, Antje Wick, Friedrich Hubertus Schmitz Winnenthal, Anne-Valerie Keller, Lilli Podola, Martin Bendszus, Dennis Riehl, Felix Sahm, Philipp Kickingereder, Christine Jungk, Christel Herold-Mende, Michael Platten, Sébastien Wieckowski, Philipp Beckhove, Wolfgang Wick |
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| Rok vydání: | 2018 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Temozolomide business.industry Immune checkpoint inhibitors Complete remission Regulatory T-Lymphocytes Repeat Surgery medicine.disease Phase i study Abstracts Internal medicine Medicine In patient Neurology (clinical) business medicine.drug Glioblastoma |
| Zdroj: | Neuro-Oncology. 20:vi9-vi9 |
| ISSN: | 1523-5866 1522-8517 |
| Popis: | BACKGROUND. VXM01 consists of the attenuated Salmonella Typhi Ty21a delivering a plasmid encoding vascular endothelial growth factor receptor 2 (VEGFR2) into the Peyer’s patches via the oral route of administration. The vaccine elicits a systemic T-cell response targeting VEGFR2. This trial examined safety and tolerability, clinical and immunogenic responses to VXM01 after at least four vaccinations at 10(6) or 10(7) colony-forming units in patients with progressive glioblastoma who have failed at least radiochemotherapy with temozolomide. METHODS. Patients with progressive operable glioblastoma were subjected to VXM01 in one oral administration each on day 1, 3, 5, and 7, and 4-weekly single doses during the tumor follow-up period after surgery. Follow-up was done by safety laboratories and physical examinations, MRI, T-cell immunomonitoring in the peripheral blood, and brain tumor immunohistochemistry. RESULTS. Fourteen patients have been treated with VXM01, three out of them with additional nivolumab. Surgery has been performed in eight patients. Under VXM01 treatment 129 adverse events, mostly unrelated to VXM01, were observed after a median of 7.5 doses per patient. IFN-γ ELISpot analysis showed a detectable VEGFR2–specific T–cell response in 7 out 12 patients measured. In the observation period up to 2 years, seven patients are alive and survived for more than 12 months. Survival correlated with a higher CD8/Treg ratio in progressive and primary tumor, which further increased after VXM01 treatment. In patients with prolonged survival a decrease in intratumoral PD-L1 was measured. In one patient, a strong partial response was observed under VXM01 monotherapy, and a complete response after addition of nivolumab. CONCLUSION: VXM01 was safe, produces detectable specific peripheral immune responses and increased T-cell infiltration in post-vaccine tumor tissue, with a favorable course of disease in five patients. A combination study of VXM01 and anti-PD-L1 avelumab in 30 patients with relapsed glioblastoma has been launched. |
| Databáze: | OpenAIRE |
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