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<p>The clonal glioma driver mutation <i>IDH1</i><sup>R132H</sup> 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<sup>+</sup> 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) <i>IDH</i>-mutant astrocytomas in a randomized phase 2 trial (ClinicalTrials.gov identifier: <a href="https://clinicaltrials.gov/ct2/show/NCT02454634">NCT02454634</a>).</p>

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IDH1-mutant vaccine in newly diagnosed astrocytoma: final analysis of the multicenter, single-arm, open-label, first-in-human phase 1 NOA16 trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • Lukas Bunse,
  • Katharina Lindner,
  • Antje Wick,
  • Angelika Freitag,
  • Lisa-Marie Lanz,
  • Dominic Edelmann,
  • Abigail Suwala,
  • Michael O. Breckwoldt,
  • Inga Harting,
  • Felix Sahm,
  • Richard F. Schlenk,
  • Anita Schmitt,
  • Oliver Schnell,
  • Jörg Hense,
  • Martin Misch,
  • Dietmar Krex,
  • Monika Denk,
  • Juliane Walz,
  • Joachim P. Steinbach,
  • Andreas von Deimling,
  • Michael Schmitt,
  • Theresa Bunse,
  • Ghazaleh Tabatabai,
  • Martin Bendszus,
  • Isabel Poschke,
  • Wolfgang Wick,
  • Michael Platten

摘要

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).