A Randomized Double-Blind Placebo-Controlled Phase II Trial of Dendritic Cell Vaccine ICT-107 in Newly Diagnosed Patients with Glioblastoma

Abstract

Purpose: To evaluate the results of the randomized, double-blind, placebo-controlled phase II clinical trial of ICT-107 in patients with newly diagnosed glioblastoma.

Patients and methods: We conducted a double-blinded randomized phase II trial of ICT-107 in newly diagnosed patients with glioblastoma (GBM) and tested efficacy, safety, quality of life (QoL), and immune response. HLA-A1⁺ and/or -A2⁺-resected patients with residual tumor ≤1 cm³ received radiotherapy and concurrent temozolomide. Following completion of radiotherapy, 124 patients, randomized 2:1, received ICT-107 [autologous dendritic cells (DC) pulsed with six synthetic peptide epitopes targeting GBM tumor/stem cell-associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL13Rα2] or matching control (unpulsed DC). Patients received induction ICT-107 or control weekly × 4 followed by 12 months of adjuvant temozolomide. Maintenance vaccinations occurred at 1, 3, and 6 months and every 6 months thereafter.

Results: ICT-107 was well tolerated, with no difference in adverse events between the treatment and control groups. The primary endpoint, median overall survival (OS), favored ICT-107 by 2.0 months in the intent-to-treat (ITT) population but was not statistically significant. Progression-free survival (PFS) in the ITT population was significantly increased in the ICT-107 cohort by 2.2 months (P = 0.011). The frequency of HLA-A2 primary tumor antigen expression was higher than that for HLA-A1 patients, and HLA-A2 patients had higher immune response (via Elispot). HLA-A2 patients achieved a meaningful therapeutic benefit with ICT-107, in both the MGMT methylated and unmethylated prespecified subgroups, whereas only HLA-A1 methylated patients had an OS benefit.

Conclusions: PFS was significantly improved in ICT-107-treated patients with maintenance of QoL. Patients in the HLA-A2 subgroup showed increased ICT-107 activity clinically and immunologically.

Figure 1.

CONSORT diagram.

Figure 2.

Study flow chart. SOC = standard of care; TMZ = temozolomide Treatment scheme is the same for all patients throughout the course of the study, regardles of treatment group (ICT-107 or Control) *Chemoradiation for 6 weeks: induction TMZ (75 mg/m²/day for 42 days) and focal radiotherapy (60 Gy in 30 fractions, 5 days/week for 6 weeks) § Administered 5 days per week for 12 months. Cycle 1: 150 mg/m²/day × 5. Cycles 2 −12: 200 mg/m²/day × 5 β Maintenance administration on day 21 of cycles 1, 3, 6, 10, coupled with maintenance TMZ. if TMZ is delayed, these vaccinations will also be delayed to ensure TMZ and vaccination cycles remain synchronized. Extended maintenance administration at cycles 16, 22 and continuing every 6 months until depletion or confirmation of PD

Figure 3.

PFS (A) and OS (B) Kaplan-Meier Curves.