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Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase I trial

ABSTRACT: Glioblastoma is a fatal disease with a median prognosis of 12-18 months. Recent studies have shown encouraging results using neoantigen-based vaccines to stimulate glioblastoma-directed immune responses, but overall immunogenicity has been low. Here, we report the results of an open-label, single-arm, phase I clinical trial (GT-20; NCT04015700) to evaluate safety and feasibility (primary endpoints), as well as immunogenicity and preliminary clinical activity (secondary endpoints) of GNOS-PV01 monotherapy, a DNA-based personalized therapeutic cancer vaccine administered following surgical resection and radiation for patients with MGMT unmethylated glioblastoma. The GT-20 study vaccinated 9 patients utilizing up to 40 neoantigens per patient (range 17- 40) without causing any serious adverse events, unexpected toxicities, or dose limiting toxicities. The vaccine induced activation and expansion of circulating peripheral T cells in all evaluated patients, except one being treated with dexamethasone. The secondary endpoint was to evaluate six-month progression-free survival and twelve-month overall survival; each observed in 66.7% of patients. Median progression-free survival was 8.5 months, median overall survival was 16.3 months, and survival at 24 months was 33%, including one long-term survivor still alive four years from the time of initial surgery. This study met the pre-specified endpoints and supports the use of GNOS-PV01 as a potentially impactful component of glioblastoma immunotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE327062 | GEO | 2026/04/06

REPOSITORIES: GEO

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