"Expectations for a vaccine to be active in this patient population were very low," said Thomas Davis, M.D., Senior Vice President and Chief Medical Officer of Celldex. "If these multiple signals for immunologic and anti-tumor activity persist in the final data, it may establish a new perspective on the potential for immunotherapy. These early results have led to the expansion cohort and we are beginning to plan additional studies of combinations that could further improve efficacy."
ReACT is a Phase 2 exploratory study designed to determine if adding rindopepimut to standard of care bevacizumab improves the outcomes for patients with EGFRvIII-positive recurrent glioblastoma across multiple measures. As originally designed, the study included 2 groups:
- Group 1 - bevacizumab naive, n= apx. 70, enrollment ongoing—patients randomized to receive either rindopepimut or KLH (administered as a control), each along with bevacizumab
- Group 2 - bevacizumab refractory, n= apx. 25, enrollment completed—patients receive rindopepimut plus bevacizumab in a single treatment arm
In August 2013, Celldex announced that enrollment had been completed in Group 2 and that, based on early evidence of anti-tumor activity, an expansion cohort of approximately 75 patients (Group 2C) would be added to better characterize the potential activity of rindopepimut in this refractory patient population. As amended, the ReACT study will enroll approximately 170 patients.
Clinical Activity Overview
Group 1- Recurrent GBM; bevacizumab naive
Interim results are available for the first 40 patients enrolled [rindopepimut + bevacizumab (n=20); control + bevacizumab n=20)]. 12 patients continue to receive treatment and 27 continue to be followed for survival. While the data continue to mature, trends toward both an overall survival (OS) and progression-free survival (PFS) benefit have been observed on the rindopepimut arm to date.
| Interim ReACT Overall Survival and Progression-free Survival Bevacizumab-Naïve Recurrent GBM
|| Rindo + Bev (n=20)
|| Control + Bev (n=20)
|| 12.0 months
|| 7.9 months
|| HR = .43 (0.13, 1.44) ; p=0.16
|| 3.7 months
|| 2.0 months
|| HR= .74 (0.34, 1.61); p=0.47
The study suggests that early development of high anti-EGFRvIII titer may be predictive of improved outcomes in this patient population, as improved survival was associated with rapid generation of a robust humoral response. All 8 patients on the rindopepimut arm that developed high titers by day 57 are still alive to date (range of 3.6+ to 17.0+ months). For the remaining 10 patients who did not develop high titers by day 57, 5 remain alive (range of 3.8+ to 12.9+ months). Consistent with the premise that EGFRvIII-positive patients fare worse than the general glioblastoma population, results to date suggest that the EGFRvIII-positive patient population had a lower OS in the Control + Bevacizumab arm than was observed in the bevacizumab registration study (AVF3708g) in recurrent glioblastoma in all-comers (7.9 months OS, ReACT vs 9.3 months OS AVF3708g).