DCVax® - Brain Phase II Clinical Trial

Development stage: A Phase II clinical trial to test the efficacy of DCVax®-Brain is currently enrolling patients. Data from two Phase I clinical trials carried out by Dr. Linda Liau at UCLA, support the overall safety of DCVax®-Brain, and suggest that DCVax®-Brain may induce an immune response. The clinical data suggest delayed time to disease recurrence and increased survival, especially in patients with stable disease at entry.

Trial design: The Phase II DCVax®-Brain clinical trial will enroll approximately 141 patients with newly diagnosed GBM and with a 2:1 ratio of treated patients to concurrent controls at 12-15 sites in the United States.

Indication: Patients with newly diagnosed Glioblastoma multiforme that require treatment with surgery, radiation and concurrent chemotherapy will be eligible for participation in this clinical trial. Other eligibility criteria include absence of measurable disease progression after completion of primary treatment.

Endpoints: The primary endpoint for the Phase II clinical trial is survival free of disease progression. The first secondary endpoint is overall survival. Other endpoints include safety and the induction of immune responses. Historical control patients in the category of newly diagnosed GBM show a median time to progression of about 8-9 months with median survival of 15-16 months. It is expected that patient accrual will be completed over 9 months and that primary endpoint data will be completed at the 21 month time point. A biological license application is expected to be submitted shortly thereafter.

Product: DCVax®-Brain is manufactured using a patient’s own dendritic cells, loaded with a tumor cell lysate prepared from surgically resected tumor tissue. The dendritic cells are generated from monocytes obtained through a single leukapheresis. The company has contracted out the manufacturing of DCVax®-Brain as well as some of the management of the clinical trial.

Immunization schedule: Immunization starts following primary therapy, i.e. surgery, radiation therapy and concurrent chemotherapy. Immunizations will be given at weeks 0, 2 and 4 and at months 2, 4, 8 and 12, 18, 24, and 30.

DCVax®-Brain is an experimental autologous cellular therapy designed to create a specific immune response against a patient’s cancer. DCVax®-Brain utilizes a patient’s own dendritic cells (DC), and an extract of the patient’s own tumor cells to achieve an immune response. The tumor from surgery is shipped to a manufacturing facility, as are blood cells, in order to prepare the DCVax®-Brain. DCVax®-Brain is then shipped frozen to the clinic for administration to the patient. DCVax®-Brain is usually manufactured in sufficient quantities for treatment of at least one year, and often for two or more years.

Previous Phase I Clinical Trials

Two Phase I clinical trials were carried out at UCLA by Dr. Linda Liau for patients with Glioblastoma multiforme (GBM). The second clinical trial is still ongoing, and focuses on newly diagnosed patients with GBM whose primary treatment included surgery, radiation and chemotherapy. Three injections of DCVax®-Brain were administered intradermally, or under the skin two weeks apart, followed for some patients with subsequent booster injections.

Data from two Phase I clinical trials on DCVax®-Brain carried out at UCLA continue to mature: investigators continue to measure the delays in disease progression and the extensions of overall survival in DCVax®-Brain treated patients who survive. To date, the clinical data have shown a median survival of 33.8 months (and continuing) for DCVax®-Brain treated patients, with 9 of 19 patients still alive from 8-82 months after initial surgery. Most of these patients have no evidence of tumor recurrence. Four of these patients have survival times without progression or recurrence of their cancer that now extends beyond 45 months.