AT-60A RANDOMIZED DOUBLE BLIND PLACEBO-CONTROLLED PHASE 2 TRIAL OF DENDRITIC CELL (DC) VACCINE ICT-107 FOLLOWING STANDARD TREATMENT IN NEWLY DIAGNOSED PATIENTS WITH GBM

BACKGROUND: This double-blinded randomized phase 2 trial of ICT-107 in newly-diagnosed glioblastoma (GBM) patients rigorously tested efficacy, safety, QoL, and immune response. METHODS: HLA-A1+ and/or -A2+ resected patients with residual tumor <1 cm3 received 6wks of concurrent temozolomide (TMZ) and radiation. 124 patients, randomized 2:1, received ICT-107 (autologous DCs pulsed with 6 synthetic peptide CTL epitopes targeting GBM tumor/stem cell-associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL-13Rα2) or matching control (unpulsed DC). Patients then received induction ICT-107 or control QWx4 followed by maintenance TMZ, 5 days/mo for 12mos. Maintenance vaccinations occurred at 1, 3, and 6mos after induction, and every 6mos thereafter until progression. RESULTS: ICT-107 was generally safe and well tolerated, with no AE imbalance between treated and control. At the 67-event trial completion, median OS had not been reached. Follow-up continues: at 79 events, median OS favored ICT-107 by 1.6mos in the ITT and 1.9mos in the PP (117 patients completing induction) groups, although not statistically significant (p = 0.64 two-sided, HR = 0.89, and p = 0.48, HR = 0.84, respectively). Median PFS was significantly improved in the ICT-107 ITT and PP groups by 2.2mos and 2.4mos (p = 0.01, HR = 0.57, p = 0.006, HR = 0.54, respectively). Treatment extended PFS with sustained QoL assessed by FACT-BR, KPS, and steroid usage. The frequency of HLA-A2 primary tumor antigen expression was higher than that for HLA-A1 patients, and HLA-A2 patients had higher vaccine response (via Elispot) than HLA-A1 patients. PP HLA-A2 patients in both the MGMT methylated and unmethylated pre-specified subgroups saw a clinically meaningful ICT-107 effect, although HLA-A1 patients received no benefit from vaccine. CONCLUSIONS: PFS was significantly improved in ICT-107 treated patients with maintenance of QoL. Patients in the HLA-A2 MGMT subgroups show stronger ICT-107 activity clinically and immunologically, and these groups will be studied in a future phase 3 trial.