IDH1-mutant vaccine in newly diagnosed astrocytoma: final analysis of the multicenter, single-arm, open-label, first-in-human phase 1 NOA16 trial
Bunse L, Lindner K, Wick A, Freitag A, Lanz LM, Edelmann D, Suwala A, Breckwoldt MO, Harting I, Sahm F, Schlenk RF, Schmitt A, Schnell O, Hense J, Misch M, Krex D, Denk M, Walz J, Steinbach JP, von Deimling A, Schmitt M, Bunse T, Tabatabai G, Bendszus M, Poschke I, Wick W, Platten M (2026)
Publication Type: Journal article
Publication year: 2026
Journal
DOI: 10.1038/s43018-026-01199-y
Abstract
The clonal glioma driver mutation IDH1R132H gives rise to a major histocompatibility class II-restricted neoepitope. A multicenter, first-in-human phase 1 trial met its prespecified primary endpoints by demonstrating safety and immunogenicity of an IDH1-R132H peptide vaccine (IDH1-vac) integrated into standard of care in 33 participants with newly diagnosed grade III and IV (World Health Organization classification 2007) IDH1-R132H+ astrocytomas (NOA16). Here we report on the clinical and immunological long-term follow-up of this trial as secondary and translational endpoints. The 8-year progression-free and overall survival (OS) rates were 0.42 months (confidence interval (CI): 0.24–0.59) and 0.66 months (CI: 0.46–0.79), respectively. For participants with grade IV astrocytoma, median OS was 106.1 months (CI: 39.6–not estimable (NE)), comparing favorably to the published median OS in this population ranging from 31.6–56.4 months. Within the responder group, sustained antibody responses to IDH1-R132H were associated with a favorable long-term clinical course. IDH1-vac-induced T cell responses were detected in the inflamed brain lesion of an IDH1-vac-associated pseudoprogression, whereas no IDH1-vac-induced T cells were found in participants with early progressive disease. The favorable long-term outcome of the NOA16 cohort supports investigating IDH1-vac in persons with newly diagnosed grade 3 and 4 (World Health Organization classification 2021) IDH-mutant astrocytomas in a randomized phase 2 trial (ClinicalTrials.gov identifier: NCT02454634).
Authors with CRIS profile
Involved external institutions
Deutsches Krebsforschungszentrum (DKFZ)
Germany (DE)
Universitätsklinikum Heidelberg
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Universitätsklinikum Carl Gustav Carus Dresden
Germany (DE)
Eberhard Karls Universität Tübingen
Germany (DE)
Senckenberg Forschungsinstitut und Naturmuseum
Germany (DE)
Germany (DE)
Universitätsklinikum Heidelberg
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Universitätsklinikum Carl Gustav Carus Dresden
Germany (DE)
Eberhard Karls Universität Tübingen
Germany (DE)
Senckenberg Forschungsinstitut und Naturmuseum
Germany (DE)
How to cite
APA:
Bunse, L., Lindner, K., Wick, A., Freitag, A., Lanz, L.M., Edelmann, D.,... Platten, M. (2026). IDH1-mutant vaccine in newly diagnosed astrocytoma: final analysis of the multicenter, single-arm, open-label, first-in-human phase 1 NOA16 trial. Nature Cancer. https://doi.org/10.1038/s43018-026-01199-y
MLA:
Bunse, Lukas, et al. "IDH1-mutant vaccine in newly diagnosed astrocytoma: final analysis of the multicenter, single-arm, open-label, first-in-human phase 1 NOA16 trial." Nature Cancer (2026).
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