A randomized, double-blind, placebo-controlled phase 2 trial of dendritic cell (DC) vaccination with ICT-107 in newly diagnosed glioblastoma (GBM) patients.

Abstract

2005 Background: The trial investigated whether adding tumor-antigen-loaded DC vaccine to surgery and chemoradiation would improve overall survival (OS) or progression free survival (PFS). Methods: HLA-A1+ and/or -A2+ resected patients with residual tumor <1 cm3 received 6 weeks of concurrent temozolomide (TMZ) and radiation. 124 patients were randomized 2:1 to receive ICT-107 (autologous PBMC-derived DC pulsed with 6 synthetic peptide CTL epitopes targeting the GBM tumor and tumor stem cell-associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL-13Rα2) or its matching control (unpulsed DC). Patients then received induction ICT-107 or control QWx4 followed by maintenance TMZ, 5 days/mo for 12 mos. Booster vaccinations occurred at 1, 3, and 6 mos after induction, and every 6 mos thereafter. The trial concluded and data were evaluated at 67 events. Results: ICT-107 was generally safe and well tolerated, with no imbalance in AEs between the treated and control groups. PFS improved by 2 mos in the ICT-107 ITT group (p=0.02 two-sided, hazard ratio (HR)=0.56). In the per-protocol (PP) group (117 patients receiving all 4 induction vaccinations), p=0.01 two-sided, HR=0.53, and the difference in median PFS increased to 3 mos. The median OS favored ICT-107 by 2 mos in the ITT and 3 mos in the PP groups. However, the number of events was small and OS did not reach statistical significance (p=0.58 two-sided, HR=0.87, and p=0.40 two-sided, HR=0.79, respectively). Median follow-up from randomization was 13.6 mos. In the ICT-107 group, vaccine activation markers IL12 and HLA-DR were predictive of OS (p-values < 0.05). There were no correlations in the placebo group. Conclusions: This is the first randomized, placebo-controlled immunotherapy trial in GBM to positively affect a clinical outcome, PFS. Although OS improvement was not statistically significant at the 67/124 event point, patients continue to be followed for OS, allowing periodic updating of the primary endpoint and assessment of long-term survival. Analysis of QOL, and correlation of both tumor antigen expression and vaccine immunologic response with OS are in process.