| Autor: |
M Platten, D Schilling, L Bunse, A Wick, T Bunse, D Riehl, E Green, K Sanghvi, I Karapanagiotou-Schenkel, I Harting, F Sahm, J Steinbach, A Weyerbrock, J Hense, M Misch, D Krex, S Setvanovic, G Tabatabai, A von Deimling, M Schmitt, W Wick |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
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| Popis: |
BACKGROUND: In preclinical studies we have defined IDH1R132H as a clonal neoantigen presented on MHC class II. A peptide vaccine encompassing IDH1R132H induces tumor-specific T helper cell responses effective in controlling syngeneic IDH1R132H-mutant tumors in humanized mouse models. MATERIAL AND METHODS: NOA-16 (NCT02454634) is a first-in-man, multicenter, phase I trial testing the safety and immunogenicity of an IDH1R132H peptide in incomplete Freund’s adjuvant in patients with newly diagnosed, IDH1R132H mutant WHO °III and °IV astrocytomas. Between September 2015 and October 2016, 32 patients were enrolled in seven German sites. 23 patients (71.9%) received radiochemotherapy with temozolomide, six patients (18.8%) received radiotherapy alone and three patients (9.4%) received temozolomide alone. RESULTS: 249 vaccines were administered, 29 (90.6%) of the patients of the safety set (N=32) and 27 (90.0%) patients of the immunogenicity set (N=30) received all eight vaccines. No regime-limiting toxicity was observed. The majority of the patients (N=29, 90.6%) experienced treatment related adverse events (trAE), 1 (3.1%) of them had treatment related SAE. None of the reported AEs were severe. 28/30 (93.3%) patients, who were evaluable for immunogenicity, displayed mutation-specific T cellular (24/30 (80%)) or humoral (26/30 patients (87%)) immune responses not detectable before vaccination. Until end of study no deaths were observed. 4/32 (12.5 %) patients had PD according to RANO criteria, all other patients (N=28, 87.5%) had SD. 12/32 (37.5%) patients displayed pseudoprogressions after the initiation of the vaccine. Single-cell T cell receptor (TCR) sequencing allowed for the identification of IDH1R132H-specific TCRs. CONCLUSION: NOA-16 met its primary endpoints by demonstrating safety and immunogenicity of a mutation-specific IDH1R132H peptide vaccine given with standard of care in patients with newly diagnosed IDH1R132H mutant malignant astrocytoma. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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