A Randomized Double-Blind Placebo-Controlled Phase 2 Trial Of Dendritic Cell Vaccine ICT-107 In Newly Diagnosed Patients With Glioblastoma.
Clinical cancer research : an official journal of the American Association for Cancer Research
PURPOSE: To evaluate the efficacy of ICT-107.
PATIENTS AND METHODS: We conducted a double-blinded randomized phase II trial of ICT-107 in newly-diagnosed glioblastoma (GBM) patients 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 (DCs) pulsed with six synthetic peptide 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 received induction ICT-107 or control weekly x 4 followed by twelve months of adjuvant temozolomide. Maintenance vaccinations occurred at one, three, and six months and every six 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 intention-to-treat (ITT) population was significantly increased in the ICT-107 cohort by 2.2 months (p=0.011). 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 pre-specified subgroups, whereas only HLA-A1 methylated patients had an OS benefit.
CONCLUSION: PFSl 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.
Wen, Patrick Y; Reardon, David A; Armstrong, Terri S; Phuphanich, Surasak; Aiken, Robert D; Landolfi, Joseph C; Curry, William T; Zhu, Jay-Jiguang; Glantz, Michael; Peereboom, David M; Markert, James; LaRocca, Renato; O'Rourke, Donald M; Fink, Karen; Kim, Lyndon; Gruber, Michael; Lesser, Glenn J; Pan, Edward; Kesari, Santosh; Muzikansky, Alona; Pinilla, Clemencia; Santos, Radleigh G; and Yu, John S, "A Randomized Double-Blind Placebo-Controlled Phase 2 Trial Of Dendritic Cell Vaccine ICT-107 In Newly Diagnosed Patients With Glioblastoma." (2019). Articles, Abstracts, and Reports. 1872.