Brain cancer vaccine succeeds at prolonging survival in Phase 3 trial

By Rachel Arthur contact

- Last updated on GMT

Pic:getty/montyrakusen
Pic:getty/montyrakusen

Related tags: Cancer vaccine, Immunotherapy, Oncology

A Phase 3 trial for Northwest Biotherapeutics’s DCVax-L vaccine extended survival in patients with gliobastoma for many months, or in some cases, years: according to new data.

In the Phase III clinical trial, both median survival and the ‘long tail’ of extended survival were increased in both newly diagnosed and recurrent glioblastoma brain cancer patients treated with DCVax-L: meaning the trial has met both the primary and the secondary endpoints of the trial.

The Bethesda, Maryland company believes this is the first time in nearly 20 years that a Phase III trial of a systemic treatment has shown such survival extension in newly diagnosed glioblastoma, and the first time in nearly 30 years that a Phase III trial of any type of treatment has shown such survival extension in recurrent glioblastoma. 

Personalized immune therapy

Glioblastoma is the most common and most lethal form of primary brain cancer.  Standard of care (SOC) treatments have been virtually unchanged for nearly 20 years.  With SOC treatments, patients typically survive for only about 15-17 months from diagnosis, with the tumor recurring at about 6-8 months from diagnosis and the patients typically surviving for about 7-9 months after recurrence.  Five-year survival from diagnosis is only about 5%.

DCVax-L is a fully personalized immune therapy made from a patient's own immune cells (dendritic cells) and antigens (biomarkers) from a sample of the patient's own tumor.  A multi-year set of doses is produced in a single manufacturing batch, which takes 8 days.  The product is then stored frozen in individual doses, and is "off the shelf" throughout the treatment regimen.  The doses are stored centrally and simply taken out of the freezer and delivered to the physician when needed for the patient's next treatment.  

In the trial, all of the participants in the trial underwent the standard treatment for glioblastoma of surgery followed by radiotherapy and chemotherapy. Patients with a new glioblastoma diagnosis who were treated with the vaccine survived 19.3 months on average from randomization (22.4 months from surgery), compared to 16.5 months for the control group. Patients with recurrent glioblastoma who were treated with the vaccine survived 13.2 months on average, compared to 7.8 months for the control group.

Thirteen percent of patients treated with the vaccine survived at least five years from diagnosis compared to 5.7 percent in the control group, with the longest survivor surpassing eight years. 

Unlike chemotherapy and radiotherapy, the vast majority of patients reported no side-effects from the immunotherapy vaccine.

Professor Ashkan, Professor of Neurosurgery at King’s College Hospital, London, and European Chief Investigator of the clinical trial, said: “Immunotherapy is a very promising approach for treating cancer, and the final results of this phase 3 trial, now unblinded and published, offer fresh hope to patients battling with glioblastoma.

“The vaccine was shown to prolong life, and interestingly so in patients traditionally considered to have poorer prognosis. For example, we see clear benefits in the older patient groups as well as in those patients in whom radical surgery was not possible for technical or other reasons.

“I am optimistic we can build upon this going forward; investigating combination of DCVax-L with other emerging therapies for glioblastomas. The long-term survivor group in particular has the potential to further teach us about the basic biology of glioblastomas, given that many patients in this group did not have the usual expected characteristics for good outcomes.

“Applying the same technology to develop treatments for other forms of brain tumors will be the natural next step.”

The Phase III trial of DCVax-L took place at 94 hospitals in four countries. The median Overall Survival (mOS) for newly diagnosed GBM patients (n=232) was 19.3 months from randomization (22.4 months from surgery) with DCVax-L vs. 16.5 months from randomization in the controls (HR=0.80, p=0.002).  Survival at 48 months from randomization was 15.7% vs. 9.9%, and at 60 months was 13% vs. 5.7%.  For recurrent GBM (n=64), mOS was 13.2 months from relapse vs. 7.8 months (HR = 0.58, p<0.001).

Survival at 24 and 30 months post-recurrence was 20.7% vs. 9.6%, and 11.1% vs 5.1%, respectively. In newly diagnosed GBM patients with methylated MGMT, mOS was 30.2 months from randomization (33 months from surgery) with DCVax-L (n=90) vs. 21.3 months in controls (n=199) (HR=0.74, p=0.027).

Out of more than 2,100 doses of DCVax-L administered during the Phase III trial, there were 5 serious adverse events that were deemed ‘at least possibly’ related to the treatment.  There were 3 cases of intracranial edema, 1 case of nausea and 1 case of lymph node infection. 

The trial results were published last week in the peer-reviewed cancer journal Jama Oncology.​ 

Northwest Biotherapeutics is currently working on preparations for applications for regulatory approval of DCVax-L.

Linda Powers, CEO of NW Bio, said: "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."

"It is especially encouraging to see these survival extensions with a treatment that has such a benign safety profile. 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."

Related topics: Bio Developments