Abstract
BACKGROUND
The Neurooncology Working Group of the German Cancer Society trial 16 (NOA16), a multicenter, single-arm, open-label, first-in-human phase I trial, met its primary endpoints in demonstrating safety and immunogenicity of a long peptide vaccine targeting IDH1(R132H) (IDH1-vac) added to standard of care in 32 patients with newly diagnosed World Health Organization (WHO) Grade 3 (n=21) and 4 (n=11) IDH1(R132H)+ astrocytomas (ClinicalTrials.gov identifier NCT02454634).
MATERIAL AND METHODS
Here, we report on the clinical and immunological long-term follow-up of NOA16. Data cut-off was May 2023.
RESULTS
Six-year progression-free and survival rates of patients in the safety data set were 0.47 (CI: 0.29 - 0.63) and 0.66 (CI: 0.46 - 0.79), respectively. Six-year progression-free and survival rates in the Grade 3 population were 0.52 (CI: 0.30 - 0.71) and 0.67 (CI: 0.43 - 0.83), respectively. Six-year progression-free and survival rates in the Grade 4 population were 0.55 (CI: 0.23 - 0.78) and 0.62 (CI: 0.28 - 0.84), respectively. Six-year progression-free and survival rates in patients with complete resection (n=17) were 0.82 (CI: 0.55 - 0.94) and 0.88 (CI: 0.61 - 0.97), respectively. Calculated via the Simon-Makuch method, patients in the immunogenicity dataset (n=30) with immune responses (IR) had six-year progression-free and survival rates of 0.46 (0.26 - 0.64) and 0.75 (CI: 0.55 - 0.87), respectively. Two patients without IR showed progressive disease (PD) within two years of first diagnosis and died within 3 years of first diagnosis. In one-year landmark analyses, best mutation-specific B cell response at the time point of last vaccination or later was associated with a favorable clinical course, suggesting a relevant but differential response to repetitive therapeutic vaccination regimes.
CONCLUSION
This data supports a randomized clinical trial of IDH-vac in patients with newly diagnosed IDH-mutant gliomas. A booster treatment regime should be considered as continuous source of IDH1R132H-reactive T cells.