The study „Targeting IDH1R132H in WHO grade III-IV IDH1R132H-mutated gliomas by a peptide vaccine – a Phase I safety, tolerability and immunogenicity multicenter trial” (NOA-16) is a first-in-man trial on the safety and immunogenicity of an IDH1 peptide vaccine in grade III-IV, IDH1R132H-mutant gliomas. The coordinating investigator is Prof. Platten, German Cancer Research Center (DKFZ) and Chairman of the Department of Neurology, University Hospital Mannheim. The trial has been initiated in June 2015. Follow-up period of the last patient was completed in September 2017.
Currently, the data management of the NCT Trial Center finalizes the last queries and plausibility checks on trial data and the statistical analysis is already in preparation. Final results are expected for spring 2018.
Within the NOA 16 trial, the IDH1 peptide vaccine – a 20mer peptide encompassing the IDH1R132H-mutated region emulsified in Montanide® – was administered to 33 patients.
The patient population is molecularly defined: IDH1R132H mutant grade III and IV gliomas without co-deletion of 1p/19q and with loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression. Patients must have received radiotherapy alone (treatment group 1), 3 cycles chemotherapy with temozolomide (TMZ; treatment group 2) or combined radiochemotherapy with TMZ (treatment group 3) prior to enrollment.
The IDH1 peptide vaccine contains the IDH1R132H peptide emulsified in Montanide® and was administered subcutaneously in combination with topical imiquimod (Aldara®) in weeks 1, 3, 5, 7, 11, 15, 19 and 23 (visits 3 10). In treatment group 1 vaccination treatment was started 4 6 weeks post radiotherapy. In treatment groups 2 and 3 vaccination treatment was done in parallel with TMZ chemotherapy starting at day 10 of the 4th TMZ cycle (treatment group 2) or at day 10 of the 1st TMZ cycle post concomitant radiochemotherapy (treatment group 3).
Primary Objectives are
- to determine safety and tolerability of repeated fixed dose vaccinations of the IDH1 peptide vaccine administered with topical imiquimod (Aldara®), and
- to assess immunogenicity of the IDH1 peptide vaccine and hence demonstrate "proof of principle" for the vaccination strategy.
Safety endpoint will be analyses for all 33 patients; 30 of these patient are evaluable for immunogenicity analyses.
The study is funded by the NCT 3.0 Trial Program and DKTK. The trial NOA-16 is a study of the German Cancer Consortium (DKTK). This trial is performed within the Neurooncology Program, Neurology Clinic and NCT at the University Hospital Heidelberg and 7 other centers in Germany, which are part of the DKTK. The trial is supported by the Neurooncology Working Group of the German Cancer Society (NOA).
The GMP manufacturing of the peptide vaccine was carried out by the GMP Core Facility, Innere Medizin V, Heidelberg University Hospital.
The NCT Trial Center comprehensively supports the NOA 16 trial by by project management, data management and biostatistics.
For details please refer to CTIS and Clinical.Trials.gov.