Multicenter phase 1 trial of adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma

Recent studies have shown encouraging results using neoantigen-based vaccines to stimulate glioblastoma-directed immune response, but overall immunogenicity has been low. The multicenter phase 1 GT-20 trial evaluated the DNA-based personalized therapeutic cancer vaccine GNOS-PV01 for MGMT unmethylated glioblastoma. The trial included nine patients who underwent surgical resection and radiation, followed by the vaccine, using up to 40 neoantigens per patient (range 17-40). No serious adverse events, unexpected toxicities, or dose-limiting toxicities were observed (primary endpoint). The vaccine induced activation and expansion of circulating peripheral T cells in all evaluated patients except one, who was being treated with dexamethasone. The secondary endpoints were 6-month progression-free survival rate and 12-month overall survival rate; both were 66.7%. Median progression-free survival was 8.5 months, median overall survival was 16.3 months and survival rate at 24 months was 33%, including one long-term survivor still alive 4 years after initial surgery. The authors conclude that these findings support the use of GNOS-PV01 as potentially impactful component of glioblastoma immunotherapy.