A dendritic cell-based immunotherapeutic vaccine increased median overall survival by about four months in a phase II placebo-controlled study in newly diagnosed glioblastoma multiforme.
When overall survival and progression-free survival were assessed in pre-specified patient subgroups, results favored treatment with the ICT-107 vaccine over control in HLA-A2 patients within each of the two major MGMT subgroups (unmethylated and methylated).
While the subgroups were small in size, and not powered to show statistical significance, the numeric advantages in favor of ICT-107 treated patients were shown to be large and clinically meaningful, according to the drug’s sponsor, ImmunoCellular Therapeutics Ltd.
The trial is a randomized, double-blind study of the safety and efficacy of ICT-107 in newly diagnosed patients with glioblastoma multiforme following resection and chemoradiation. ICT-107 is an intradermally administered autologous vaccine consisting of the patient’s dendritic cells pulsed with six synthetic tumor-associated antigens: AIM-2, MAGE-1, TRP-2, gp100, HER-2, IL-13R 2. The control consists of the patient’s unpulsed dendritic cells. The study was presented at the annual meeting of the American Society for Clinical Oncology in Chicago.
A total of 124 patients were randomized at 25 clinical trial sites in the U.S. All patients in the trial received standard-of-care temozolomide. The regimen is four induction doses of ICT-107 after chemoradiation, and then maintenance doses until the patient progresses.
The primary endpoint of the trial is OS. Other secondary endpoints include the rates of OS and PFS at six months after surgery, then assessed every three months until the end of the study. Safety and immune response are additional secondary endpoints. The subgroups analyzed in the phase II trial were based on age, gender, HLA type, MGMT status, performance status and resection status.
In the per-protocol analysis of data from HLA-A2 patients with unmethylated MGMT, the control and treated median OS times were 11.8 and 15.8 months, respectively, indicating about a 33 percent numeric survival increase for treated patients (HR=0.612, log-rank p-value=0.175).
The median PFS times for control and treated patients were 6.0 and 10.5 months, respectively, indicating about a 4.5-month or 75 percent numeric PFS increase for treated patients (HR=0.758, log-rank p-value=0.442).
In the per-protocol analysis of data from HLA-A2 patients with methylated MGMT, the control and treated groups had still not reached median survival times as of the time of data analysis, with the majority of patients still alive (65 percent of treated compared to 57 percent of control patients). However, the median PFS times for control and treated patients were 8.5 and 24.1 months, respectively, indicating about a 15.6-month or 184 percent statistically significant PFS increase for treated patients (HR=0.259, log-rank p-value=0.005).
ImmunoCellular is in the process of finalizing the design of the phase III protocol, in anticipation of discussions with the FDA and the European Medicines Agency. Plans are underway to request an end-of-phase II meeting with the FDA, anticipated to take place during the summer, according to the sponsor.
