A phase I trial has demonstrated that an adjuvant personalized DNA vaccine is safe and shows promising efficacy in patients with MGMT-unmethylated glioblastoma. The study, published in Nature Cancer by Tanner M. Johanns, MD, PhD, of Washington University School of Medicine in St. Louis, and colleagues, reported no serious adverse events and extended overall survival for the nine participants compared with historical outcomes.
Specifically, the median overall survival was 16.3 months, with a 24-month survival rate of 33%, notably including one long-term survivor still alive four years post-initial surgery. Median progression-free survival (PFS) stood at 8.5 months, achieving a 6-month PFS rate of 66.7%. The authors emphasized that “personalized 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.”
Co-author Albert H. Kim, MD, PhD, also from Washington University School of Medicine, highlighted that typically only 10% to 15% of patients with this cancer survive beyond two years. While acknowledging the trial’s small size, Kim noted that the 33% two-year survival rate “suggests a signal.” He described glioblastoma as an exceptionally challenging cancer, with an average median survival of about 18 months. The MGMT-unmethylated subgroup, specifically targeted by this vaccine, presents an even worse prognosis due to its unresponsiveness to chemotherapy, underscoring the critical need for new treatments. Unlike many other cancers, glioblastoma has not responded well to immune checkpoint inhibitors, partly because it is often characterized as “immune cold,” making it difficult to activate the immune system effectively. This vaccine offers a novel approach by targeting neoantigens—tumor-specific antigens unique to each patient’s cancer cells that the immune system can recognize. Kim expressed optimism, stating, “Transformation, I think, is also just around the corner for glioblastoma patients.”
Johanns and colleagues developed the personalized DNA vaccine by sampling individual patient tumors from multiple sites to identify up to 40 neoantigens, aiming to broaden the immune response. The study’s nine patients had a median age of 59, with 67% male and all being white. They typically received vaccine injections approximately 10 weeks after surgery and radiation. The regimen involved injections every three weeks for nine weeks, followed by every nine weeks for as long as patients participated, with a median of four doses administered. No unexpected or dose-limiting toxicities were reported; most adverse events were mild (grade 1) and localized to injection sites. All but one patient, who was on an immune-suppressing steroid, demonstrated increased immune cell activity, indicating a positive response to the vaccine.
Currently, another phase I trial is underway, assessing this personalized neoantigen DNA-based vaccine in combination with PD-1 blockade therapy for newly diagnosed MGMT promoter-unmethylated glioblastoma patients.
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