by Dr. C.H. Weaver M.D. updated 6/2019
Northwest Biotherapeutics, developer of DCVax® personalized immune therapies for solid tumor cancers, initially published interim blinded survival data from its Phase 3 clinical trial of DCVax®-L for newly diagnosed Glioblastoma brain cancer. The data were published with 69 co-authors in the peer reviewed Journal of Translational Medicine (JTM).
Unfortunately new data from this and other trails evaluating SurVax in GBM were not updated at the 2019 American Society of Clinical Oncology meetings in June.
A report evaluating SurVaxM in 63 patients enrolled at five U.S. cancer centers was however released. Patients received one 500 mcg dose of SurVaxM along with 100 mcg sargramostim after resection and chemoradiotherapy, followed by four biweekly doses with adjuvant temozolomide and then maintenance dosing every 12 weeks.
Twelve-month OS from the time of diagnosis was 93.5% in the overall population, 96.9% in the methylated MGMT group and 89.4% in the unmethylated group.
The pivotal phase III trial is ongoing while the data continues to mature, and the Company, the investigators and patients all remain blinded. The interim data set forth in the JTM publication are blinded aggregate data which include patients from both arms of the trial combined: the arm with 2/3 of the patients, who received standard of care plus DCVax-L, and the arm with 1/3 of the patients, who received standard of care plus a placebo. When the patients experienced tumor recurrence, all patients from both arms were allowed to cross over and start receiving DCVax-L, but without being unblinded as to what they had received before tumor recurrence. The patient population enrolled in the trial is similar to that in other recent trials, and more than 75% of the patients were over 50 years old (a factor associated with less favorable outcomes).
Due to the crossover design, nearly 90% of the total 331 patients in the trial have received DCVax-L treatment. For the total 331 patients (both arms of the trial combined) the median survival as of this analysis was 23.1 months from surgery. With the standard of care (SOC) today (surgery, radiation and chemotherapy), median survival for newly diagnosed Glioblastoma is 15-17 months.
For patients with methylated MGMT gene status (131 patients), median survival was 34.7 months from surgery. With standard of care today, median survival for these patients has been reported in the literature as 21.7 months. For patients with unmethylated MGMT gene status (162 patients), the median survival was 19.8 months from surgery. With standard of care today, the median survival for these patients has been reported in the literature as 12.7 months. (MGMT data was not available for 38 patients.)
The top 100 patients (30%) of the total 331 patients in the trial showed particularly extended survival, with median survival of 40.5 months from surgery. This extended survival was not fully explained by known prognostic factors such as age younger than 50 years, methylated MGMT gene status and complete resection (surgical removal) of all of the tumor. Only 8% of these 100 patients had the favorable status on all 3 of these prognostic factors.
With immune therapies, the “long tail” of the survival curve is of particular importance and focus. In this DCVax-L trial, patients who survive past certain time points, have continued onwards to substantially extended survival. The patients are continuing to move through time points based upon when they had their surgery, and only some of the patients had reached certain time points in this trial as of this analysis. For example, 223 patients were ≥30 months past their surgery date as of this analysis; 67 of these (30.0%) have lived ≥30 months and these patients have Kaplan-Meier (KM)-derived median survival estimate of 46.5 months. Also, as of this analysis, 182 patients were ≥36 months past their surgery date; 44 of these (24.2%) have lived ≥36 months and these patients have KM-derived median survival estimate of 88.2 months.
The administration of DCVax-L involves only an intra-dermal injection in the arm, similar to a flu shot, 3 times in the first month of treatment, 3 additional times over the rest of the first year (at months 2, 4 and 8), and twice a year thereafter. It thereby involves only a minimal burden on the patient.
DCVax-L has shown an excellent safety profile in the trial. The DCVax-L product has been administered well over 2,000 times, and only 7 of the 331 patients (2.1%) have experienced a serious adverse event that was deemed at least possibly related to the treatment. The rate of total adverse events (including non-serious events) was comparable to the rate of adverse events with standard of care alone.
The reported data are from the most recent prior full data collection in 2017 The Company is undertaking another full data collection, which is a multi-month process and will be continuing over the coming months.
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