In a double-blind phase II clinical trial, 124 HLA-A1+ and/or -A2+ patients with newly-diagnosed, resected glioblastoma were randomized 1:2 to intradermally receive placebo or ICT-107, a vaccine consisting of autologous DCs pulsed with six epitopes (MAGE-1, HER-2, AIM-2, TRP-2, gp100, IL-13Rα2). The vaccine was well tolerated. ICT-107 statistically significantly increased PFS by 2.2 months, with maintenance of quality of life, but did not increase OS. HLA-A2+ patients had higher tumor antigen expression and higher immune response than HLA-A1+ patients, leading to longer survival.

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-13Ralpha2) 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.

Author Info: (1) Center For Neuro-Oncology, Dana-Farber Cancer Institute (2) Center for Neuro-Oncology, Dana-Farber Cancer Institute. (3) Neuro-Oncology Branch, National Canc

Author Info: (1) Center For Neuro-Oncology, Dana-Farber Cancer Institute (2) Center for Neuro-Oncology, Dana-Farber Cancer Institute. (3) Neuro-Oncology Branch, National Cancer Institute. (4) Neuro-Oncology, Barrows Neurological Institute. (5) Medicine, Rutgers University. (6) HMH JFK Neuroscience Institute, JFK Medical Center. (7) Department of Neurosurgery, Massachusetts General Hospital / Harvard Medical School. (8) Neurosurgery, University of Texas Health Science Center at Houston, McGovern Medical School. (9) Neurosurgery, Penn State College of Medicine. (10) Brain Tumor/Neuro-Oncology center, Cleveland Clinic. (11) Surgery, University of Alabama at Birmingham. (12) Cancer Medicine, Norton Cancer Institute. (13) Department of Neurosurgery, University of Pennsylvania. (14) Neurology, Baylor Scott and While Neuro-Oncology Assoc. (15) Radiation Oncology Branch, NCI, National Institute of Health. (16) New York University. (17) Wake Forest University School of Medicine, Wake Forest Baptist Comprehensive Cancer Center. (18) Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center. (19) Department of Neurosciences and Neurotherapeutics, John Wayne Cancer Institute. (20) Cancer Center, Massachusetts General Hospital. (21) Immunology, Torrey Pines Institute For Molecular Studies. (22) Torrey Pines Institute For Molecular Studies. (23) Neurosurgery, Cedars-Sinai Medical Center.