Personalized neoantigen-pulsed autologous dendritic cells in newly-diagnosed glioblastoma: a phase Ib trial

Newly-diagnosed glioblastoma (nGBM) remains a significant unmet need with limited therapeutic options. Here, we present the results of a single-arm, open-label phase 1b trial on neoantigen-pulsed autologous dendritic cells (ZSNeo-DC) as an adjuvant treatment for nGBM. The primary endpoint was safety, as assessed by the incidence and severity of adverse events (AEs). Eleven patients with nGBM received intradermal administration of ZSNeo-DC following surgery and standard radio-chemotherapy. Treatment was well tolerated, with AEs predominantly grade 1 or 2; only two grade-1/2 febrile AEs were recorded as treatment-related. Secondary endpoint analysis showed that median progression-free survival (PFS) was 16.2 months, median overall survival (OS) was not reached, and 12-month OS rate was 100% from surgery. A range of 1.9- to 284.7-fold (median: 7.2-fold) and 0.7- to 507.0-fold (median: 10.3-fold) increase of peripheral neoantigen-specific immune response (NSIR) was observed respectively after the 3^rd and 5^th vaccination. Following vaccination, both the activated-to-exhausted ratio of effector/central memory T cells and the clonal evenness of the T cell receptor repertoire increased significantly in peripheral blood; these parameters positively correlated with NSIR and PFS. Overall, ZSNeo-DC exhibits a favorable safety profile and preliminary efficacy signals in nGBM, supporting phase 2 evaluation in expanded cohorts. Trial number: NCT04968366.