Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial
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 .
Authors
- Srestha Chattopadhyay
- Konstantina Stavroulaki
- Joann Peters
- Sarah Rochestie
- Joshua L. Dowling (ORCID: https://orcid.org/0000-0002-0340-7493)
- Niranjan Y. Sardesai (ORCID: https://orcid.org/0000-0001-6920-1167)
- Jasreet Hundal (ORCID: https://orcid.org/0000-0002-2584-5320)
- Michael R. Chicoine (ORCID: https://orcid.org/0000-0002-0689-8603)
- Gue Su Chang
- Alexandra J. Livingstone (ORCID: https://orcid.org/0000-0001-5471-4576)
- Michael D. McLellan (ORCID: https://orcid.org/0000-0002-2703-8784)
- Jaye Navarro
- Sophia A. Paxton
- Gregory J. Zipfel
- Omar H. Butt
- Jon T. Willie
- Milan G. Chheda
- Malachi Griffith (ORCID: https://orcid.org/0000-0002-6388-446X)
- Elizabeth A. R. Garfinkle (ORCID: https://orcid.org/0000-0002-7292-4347)
- Gavin P. Dunn
- Jian L. Campian
- Ryan C. Gimple
- Albert H. Kim
- S. Peter Goedegebuure
- William E. Gillanders (ORCID: https://orcid.org/0000-0002-0465-3071)
- Katherine E. Miller (ORCID: https://orcid.org/0000-0003-1054-0476)
- Obi L. Griffith (ORCID: https://orcid.org/0000-0002-0843-4271)
- Elaine R. Mardis (ORCID: https://orcid.org/0000-0002-5892-1553)
- Alfredo Perales-Puchalt
- Jian Yan
- Kaleigh F. Roberts (ORCID: https://orcid.org/0000-0001-6483-9153)
- Christopher A. Miller
- Neil Cooch
- Beth Junker
- Tanner M. Johanns (ORCID: https://orcid.org/0000-0003-1094-1528)
- Renzo Perales-Linares (ORCID: https://orcid.org/0000-0001-5309-8249)
Institutions
- James S. McDonnell Foundation (US)
- Nationwide Children's Hospital (US)
- Harvard University (US)
- Washington University in St. Louis (US)
- Massachusetts General Hospital (US)
- Bioprocess Control (Sweden) (SE)
- Mayo Clinic in Arizona (US)
- Io Therapeutics (United States) (US)
- The Ohio State University (US)
- University of Missouri (US)
Publication Details
- Journal
- Nature Cancer
- Published
- 2026-05-12
- DOI
- https://doi.org/10.1038/s43018-026-01163-w
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00