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Peer-reviewedCC BY-NC-NDNature Cancer

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

  • Elizabeth A.R. Garfinkle1
  • Renzo F. Perales-Linares2
  • Ryan C. Gimple3
  • Alexandra J. Livingstone4
  • Kaleigh F. Roberts5
  • Omar Hameed Butt4,6
  • S. Peter Goedegebuure7,6
  • Michael D. McLellan8
  • Gue Su Chang8
  • Jasreet Hundal8
  • Jian Yan2
  • Jaye B. Navarro1
24 more authors
  • Sophia A. Paxton9,1
  • Srestha Chattopadhyay10,1
  • Neil S. Cooch2
  • Alfredo Perales‐Puchalt2
  • Konstantina Stavroulaki11
  • Sarah Rochestie2
  • Joann Peters2
  • Beth Junker12
  • Jian Li Campian13
  • Milan G. Chheda3,6
  • Michael R. Chicoine14
  • Albert H. Kim15,6
  • Jon Timothy Willie15
  • Gregory Joseph Zipfel15,6
  • Joshua L. Dowling15,6
  • Christopher A. Miller16,3,8
  • Obi L. Griffith16,3,8
  • Malachi Griffith16,3,8
  • William E. Gillanders17
  • Katherine E. Miller18,1
  • Elaine R. Mardis18,1
  • Niranjan Y. Sardesai2
  • Gavin P. Dunn19
  • Tanner Michael Johanns20,21,22
22 affiliations
  1. 1The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA
  2. 2Geneos Therapeutics, Philadelphia, PA, USA
  3. 3Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
  4. 4Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA
  5. 5Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
  6. 6The Brain Tumor Center at Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA
  7. 7Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA
  8. 8McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA
  9. 9Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, OH, USA
  10. 10The Ohio State University, Columbus, OH, USA
  11. 11Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA
  12. 12BioProcess Advantage LLC, Westfield, NJ, USA
  13. 13Department of Neurology, Mayo Clinic, Rochester, MN, USA
  14. 14Department of Neurosurgery, University of Missouri, Columbia, MO, USA
  15. 15Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, USA
  16. 16Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
  17. 17Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
  18. 18Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
  19. 19Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  20. 20Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Program, Washington University School of Medicine, St. Louis, MO, USA. [email protected]
  21. 21Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA. [email protected]
  22. 22The Brain Tumor Center at Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA. [email protected]
Open at sourceDOICite

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 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 .

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Cite

BibTeXRIS
BibTeX
@article{garfinkle2026adjuvant,
  title = {{Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial}},
  author = {Elizabeth A.R. Garfinkle and Renzo F. Perales-Linares and Ryan C. Gimple and Alexandra J. Livingstone and Kaleigh F. Roberts and Omar Hameed Butt and S. Peter Goedegebuure and Michael D. McLellan and Gue Su Chang and Jasreet Hundal and Jian Yan and Jaye B. Navarro and Sophia A. Paxton and Srestha Chattopadhyay and Neil S. Cooch and Alfredo Perales‐Puchalt and Konstantina Stavroulaki and Sarah Rochestie and Joann Peters and Beth Junker and Jian Li Campian and Milan G. Chheda and Michael R. Chicoine and Albert H. Kim and Jon Timothy Willie and Gregory Joseph Zipfel and Joshua L. Dowling and Christopher A. Miller and Obi L. Griffith and Malachi Griffith and William E. Gillanders and Katherine E. Miller and Elaine R. Mardis and Niranjan Y. Sardesai and Gavin P. Dunn and Tanner Michael Johanns},
  journal = {Nature Cancer},
  year = {2026},
  month = may,
  doi = {10.1038/s43018-026-01163-w},
  url = {https://doi.org/10.1038/s43018-026-01163-w},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial
AU  - Elizabeth A.R. Garfinkle
AU  - Renzo F. Perales-Linares
AU  - Ryan C. Gimple
AU  - Alexandra J. Livingstone
AU  - Kaleigh F. Roberts
AU  - Omar Hameed Butt
AU  - S. Peter Goedegebuure
AU  - Michael D. McLellan
AU  - Gue Su Chang
AU  - Jasreet Hundal
AU  - Jian Yan
AU  - Jaye B. Navarro
AU  - Sophia A. Paxton
AU  - Srestha Chattopadhyay
AU  - Neil S. Cooch
AU  - Alfredo Perales‐Puchalt
AU  - Konstantina Stavroulaki
AU  - Sarah Rochestie
AU  - Joann Peters
AU  - Beth Junker
AU  - Jian Li Campian
AU  - Milan G. Chheda
AU  - Michael R. Chicoine
AU  - Albert H. Kim
AU  - Jon Timothy Willie
AU  - Gregory Joseph Zipfel
AU  - Joshua L. Dowling
AU  - Christopher A. Miller
AU  - Obi L. Griffith
AU  - Malachi Griffith
AU  - William E. Gillanders
AU  - Katherine E. Miller
AU  - Elaine R. Mardis
AU  - Niranjan Y. Sardesai
AU  - Gavin P. Dunn
AU  - Tanner Michael Johanns
PY  - 2026
DA  - 2026/05/12
JO  - Nature Cancer
DO  - 10.1038/s43018-026-01163-w
UR  - https://doi.org/10.1038/s43018-026-01163-w
AB  - 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 .
SN  - 2662-1347
ER  -