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 1 clinical trial (GT-20) to evaluate the 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 nine patients, using 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 who was being treated with dexamethasone. The secondary endpoint was to evaluate 6 month progression-free survival and 12 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 4 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. ClinicalTrials.gov: NCT04015700 . Johanns and colleagues report the results (including safety, efficacy and immunogenicity) of a phase 1 clinical trial of a DNA-based personalized therapeutic cancer vaccine administered following surgical resection and radiation in patients with MGMT unmethylated glioblastoma.
Garfinkle et al. (2026) studied this question.