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

Abstract

TPS2082Background: Mutations in the gene for isocitrate dehydrogenase type 1 frequently occur in diffuse gliomas resulting in a point mutation (IDH1R132H) in most of the cases. Preclinical studies have shown that mutation-specific T helper (Th) cell responses spontaneously occur in patients with IDH1-mutated gliomas and that a peptide vaccine encoding IDH1R132H is therapeutic in a humanized mouse tumor model. Methods: NOA-16 (ClinicalTrials.gov Identifier: NCT02454634) is a multicenter, first-in-man, phase I clinical trial, which is planned to enroll 39 patients with newly diagnosed malignant astrocytomas with IDH1R132H mutations at eight German sites. The target population is molecularly enriched for an unfavorable prognosis within the IDH1-mutated subgroup by mandating (i) absence of co-deletion of 1p/19q and (ii) loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression. Patients aged ≥ 18 years with a Karnofsky performance score of ≥ 70 will receive radiotherapy only (cohort 1),...