lunes, 6 de enero de 2014

Novel Vaccine Fails to Extend Survival in Glioblastoma

After very promising results in a phase 1 trial, a follow-up phase 2 randomized trial of a novel vaccine failed to meet its primary endpoint of overall survival in glioblastoma multiforme. Much to the disappointment of both the medical community and stakeholders, patients treated with the investigational ICT-107 vaccine (under development by ImmunoCellular Therapeutics) survived only about 2 to 3 months longer compared with those who received placebo, and the difference was not statistically significant.
The differences in the overall survival Kaplan-Meier curves did not reach statistical significance in the intent-to-treat population (the primary endpoint; P = 0.58, 2-sided; hazard ratio [HR], 0.87) or in the per protocol population (P = .40, 2-sided; HR, 0.79), according to the manufacturer.
However, the company notes that progression-free survival was improved in patients who received the vaccine. There was a statistically significant difference in the Kaplan-Meier curves that favored ICT-107 (P = .014, 2-sided; HR, 0.56) in the intent-to-treat population of all study participants.
Patients receiving the vaccine had a median progression-free survival time that was 2 months longer than those in the placebo group. For the per protocol population (117/124 patients who received at least 4 induction vaccinations), the Kaplan-Meier comparison P-value improved in treated patients to 0.0074 (2-sided; HR, 0.53). The median progression-free survival time increased to 3 months in the group receiving the vaccine.
"The progression-free survival data look promising in this study," commented study investigator Patrick Wen, MD, director of the Center for Neuro-Oncology at the Dana Farber Cancer Institute, Boston, Massachusetts.
"To my knowledge, this is the first time a placebo-controlled immunotherapy trial in glioblastoma has demonstrated a statistically significant improvement in a clinically relevant measure, such as progression-free survival. We await additional data to evaluate the effect on overall survival," said Dr. Wen in a statement.
Dramatic Early Results
The ICT-107 is an autologous vaccine that consists of a patient's dendritic cells pulsed with 6 peptides from tumor-associated antigens: AIM-2, TRP-2, HER2/neu, IL-13Ra2, gp100, and MAGE1. As previously reported by Medscape Medical News, the results of the phase 1 trial suggested that the vaccine may be able to dramatically extend survival. The usual median survival in these patients is around 15 months, but in this study, 8 of 16 patients had survived longer than 5 years after diagnosis. In addition, 7 participants were still alive at the time the study was published, with the length of survival ranging from 60.7 to 82.7 months after diagnosis.
Study Details
The current phase 2 trial is a randomized, double-blind, placebo-controlled phase study that evaluated the safety and efficacy of ICT-107 in newly diagnosed patients with glioblastoma multiforme. All patients had undergone surgical resection and chemoradiation.
The cohort included 124 patients who were randomly assigned to the vaccine or control at 25 clinical trial sites in the United States. Of this group, 81 patients received the ICT-107 vaccine and all received the standard-of-care temozolamide (Temodar, Merck Sharp & Dohme Corp).
The regimen consisted of 4 induction doses of ICT-107 after chemoradiation and then maintenance doses until disease progression. The primary endpoint of trial was overall survival, whereas secondary endpoints included progression-free survival and safety and immune response. The trial was powered at 80% to show a 9-month overall survival benefit assessed after reaching 64 events.
The manufacturer notes that patients who have not yet progressed will continue in the trial until an appropriate termination point can be determined.
Next Steps
Andrew Gengos, chief executive officer of ImmunoCellular Therapeutics, says that even though the trial missed its primary endpoint, it is "encouraging that the overall survival and progression-free survival results are consistent and that most of the predefined secondary endpoints in the overall survival subgroups numerically favor ICT-107 over placebo, although none has reached statistical significance."
In a statement, he notes that these results, together with the phase 1 results that indicated the potential for long-term survival, "support our view that ICT-107 has a biological and clinically relevant effect in GBM, and potentially may provide a long-term survival benefit."
The company plans on analyzing these results further, to learn more with the "goal of informing our next development and regulatory steps," he says.

ImmunoCellular also anticipates presenting the results of this trial at an upcoming national scientific or medical forum.

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