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<p>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: <a href="https://clinicaltrials.gov/study/NCT04015700">NCT04015700</a>.</p>

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Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月12日

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  • Elizabeth A. R. Garfinkle,
  • Renzo Perales-Linares,
  • Ryan C. Gimple,
  • Alexandra J. Livingstone,
  • Kaleigh F. Roberts,
  • Omar H. Butt,
  • S. Peter Goedegebuure,
  • Michael D. McLellan,
  • Gue Su Chang,
  • Jasreet Hundal,
  • Jian Yan,
  • Jaye B. Navarro,
  • Sophia A. Paxton,
  • Srestha Chattopadhyay,
  • Neil Cooch,
  • Alfredo Perales-Puchalt,
  • Konstantina Stavroulaki,
  • Sarah Rochestie,
  • Joann Peters,
  • Beth Junker,
  • Jian L. Campian,
  • Milan G. Chheda,
  • Michael R. Chicoine,
  • Albert H. Kim,
  • Jon T. Willie,
  • Gregory J. Zipfel,
  • Joshua L. Dowling,
  • Christopher A. Miller,
  • Obi L. Griffith,
  • Malachi Griffith,
  • William E. Gillanders,
  • Katherine E. Miller,
  • Elaine R. Mardis,
  • Niranjan Y. Sardesai,
  • Gavin P. Dunn,
  • Tanner M. Johanns

摘要

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.