Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase I trial [bulk TCR-seq]

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.