TOMADO DE Medscape ONCOLOGY
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.
