In a small phase 1 trial, researchers found that an adjuvant personalised DNA vaccine was safe and demonstrated promising efficacy among patients with MGMT-unmethylated glioblastoma, reports MedPage Today.
The vaccine caused no serious adverse events and extended overall survival in the nine patients included in the study compared with historical outcomes, reported Tanner Johanns, MD, PhD, of Washington University School of Medicine in St Louis, and colleagues in Nature Cancer.
Specifically, median overall survival was 16.3 months and the survival rate at 24 months was 33%, including one long-term survivor who was still alive four years from the time of initial surgery.
Median progression-free survival (PFS) was 8.5 months, with a six-month PFS rate of 66.7%.
“This study demonstrates that personalised neoantigen DNA-based vaccines can provide a potential adjuvant therapeutic option for patients with (glioblastoma), with encouraging outcomes as demonstrated by one-third of patients surviving 24 months or longer,” the authors wrote.
Co-author Albert Kim, MD, PhD, also of Washington University School of Medicine, told MedPage Today that only about 10% to 15% of patients with this cancer survive up to two years.
“The trial was small, so I don’t want to oversell, but I think (the two-year survival rate of 33%) suggests a signal,” he said.
“Glioblastoma is a very challenging cancer,” Kim added. “If you take all-comers, the median survival is somewhere around a year and a half. And there’s a subset of these glioblastoma patients – MGMT-unmethylated – who won’t respond to chemotherapy. That MGMT-unmethylated subgroup does even worse. So, this is a bad disease, and it needs an urgent set of solutions.”
Kim pointed out that while immune checkpoint inhibitors have transformed the treatment of many cancer types, they haven’t really worked in glioblastoma.
“There are various reasons for that,” he noted. “Unlike melanoma and other cancers, glioblastoma is probably what people would describe as ‘immune cold’. So, it’s just more difficult to fire up the immune system against glioblastoma. This vaccine is a way around that.”
The vaccine targets neoantigens – tumour-specific antigens unique to an individual patient’s cancer cells that their immune cells can recognise.
Kim suggested that, as with pancreatic cancer – another historically challenging cancer to treat – transformative therapies are becoming available for glioblastoma.
“It happened with melanoma 10 or 15 years ago,” he pointed out. “When I met a melanoma patient at that time, that person was dead in six months – that was the prognosis if you had a brain metastasis for melanoma. Then, a couple of years later, you had Jimmy Carter, whose melanoma had metastasised to his brain when he was 90, living to 100.
“Transformation, I think, is also just around the corner for glioblastoma patients,” he said.
Johanns and colleagues sampled a patient’s tumour at multiple sites and then designed a personalised DNA vaccine containing up to 40 neoantigens with the objective of broadening the immune response.
Among the nine patients, median age was 59, and 67% were male, and 100% were white. They received injections of the vaccine, on average, about 10 weeks after undergoing surgery and radiation treatments. The vaccine was then administered every three weeks for a nine-week period, and then every nine weeks thereafter as long as patients were able to participate.
A median of four doses was given to each patient. There were no unexpected toxicities or dose-limiting toxicities reported in the study cohort, and most of the reported adverse events were grade 1 and related to injection-site reactions.
All of the patients except one who were taking an immune-suppressing steroid showed an increase in immune cell activity, indicating a response to the vaccine.
An Ongoing phase 1 trial is also assessing the personalised neoantigen DNA-based vaccine in combination with PD-1 blockade therapy for patients with newly diagnosed MGMT promoter-unmethylated glioblastoma.
Study details
Adjuvant personalised multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial
Elizabeth Garfinkle, Renzo Perales-Linares, Ryan Gimple et al.
Published in Nature Cancer on 12 May 2026
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 personalised 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.
MedPage Today article – Personalised DNA Vaccine Shows Promise in Brain Cancer (Open access)
See more from MedicalBrief archives:
Immunotherapy combination shows early promise in glioblastoma
Personalised glioblastoma vaccine may increase long-term survival