OS6.4 NOA-16: A first-in-man multicenter phase I clinical trial of the German Neurooncology Working Group evaluating a mutation-specific peptide vaccine targeting IDH1R132H in patients with newly diagnosed malignant astrocytomas. (19th September 2018)

• Record Type: Journal Article
• Authors: Platten, M; Schilling, D; Bunse, L; Wick, A; Bunse, T; Riehl, D; Green, E; Sanghvi, K; Karapanagiotou-Schenkel, I; Harting, I; Sahm, F; Steinbach, J; Weyerbrock, A; Hense, J; Misch, M; Krex, D; Setvanovic, S; Tabatabai, G; von Deimling, A; Schmitt, M; Wick, W
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 3
• Page Start: iii226
• Page End: iii227
• Publication Date: 2018-09-19
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy139.041
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: 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.