DCVax-L was well tolerated and prolonged survival in patients with newly diagnosed and recurrent glioblastoma within the phase 3 trial.
Patients with newly diagnosed and recurrent glioblastoma (GBM) brain cancer had an increase in median survival and extended survival when treated with dendritic cell vaccination (DCVax-L), according to findings from a phase 3 clinical trial.1
Results published in JAMA Oncology showed that the trial met both the primary and secondary end points of overall survival (OS) under the statistical analysis plan for the trial.
According to NorthWest Biotherapeutics, this is the first time in close to 20 years that survival extension in patients with newly diagnosed GBM have had a survival extension in a phase 3 trial of a systemic treatment. Additionally, it is the first in nearly 30 years for a phase 3 trial examining any type of treatment to show such promising extensions in survival in this patient population.
"We are excited to see the meaningful survival extensions in glioblastoma patients treated with DCVax-L in this trial – particularly in the "long tail" of the survival curve, where we see more than double the survival rates as with existing standard of care. With well over 400 clinical trials for glioblastoma having failed over the last 15 years, it is gratifying to be able to offer new hope to patients who face this devastating disease," said Linda F. Powers, chief executive officer of NorthWest Biotherapeutics, in the press release.
DCVax-L is a fully personalized immunotherapy made from dendritic cells and biomarkers from a sample of the patient's tumor.
The prospective, externally controlled, non-randomized, phase 3 trial of DCVax-L enrolled 331 patients across 94 hospitals in 4 countries. Investigators compared OS in patients with newly diagnosed GBM and recurrent GBM treated with DCVax-L plus standard of care compared with contemporaneous matched external control patients treated with standard of care.2
Enrollment was open to patients aged 18-70 years old with newly diagnosed GBM, a Karnofsky performance score of 70 or greater, a life expectancy of 8 or more weeks, and adequate laboratory values.
The primary and secondary end points of the study were to compare OS in patients with newly diagnosed GBM and recurrent GBM with contemporaneous matched external control populations from the control groups previous randomized clinical trials.
Findings showed that the median OS for patients with newly diagnosed GBM (n = 232) was 19.3 months from randomization and 22.4 months from the time of surgery with DCVax-L vs 16.5 months from randomization in the control arm (HR, 0.80; P = .002).
At 48 months from randomization, survival was 15.7% vs 9.9%. At 60 months, rates were 13% vs 5.7%. For patients with recurrent GBM (n = 64), the median OS was 13.2 months from relapse compared with 7.8 months (HR, 0.58; P < .001). Further, the survival rates at 24 and 30 months post-recurrence were 20.7% vs 9.6%, and 11.1% vs 5.1%, respectively.
In patients with newly diagnosed GBM with methylated O6-methylguanine-DNA methyltransferase, the median OS was 30.2 months from randomization and 33 months from surgery with DCVax-L (n = 90) compared with 21.3 months the control arms (n = 199; HR, 0.74; P = .027).
Regarding safety, out of more than 2,100 doses of DCVax-L administered, only 5 serious adverse events were deemed at least possibly related to the treatment, including 3 cases of intracranial edema, 1 case of nausea, and 1 case of lymph node infection.
Overall, this study showed that the addition of DCVax-L to the standard of care treatment led to a clinically meaningful and statistically significant extension of survival for patients with both newly diagnosed GBM and recurrent GBM.
"It is especially encouraging to see these survival extensions with a treatment that has such a benign safety profile," added Powers, in the press release. "Over 2,100 doses of DCVax-L were administered during the trial, and we found that the adverse event profile was not meaningfully different than with standard of care alone. DCVax-L is also quite simple for the physician and patient: just an intradermal injection in the upper arm, 6 times over the course of year 1, and then twice a year for maintenance thereafter."