Phase II findings have shown a substantial improvement in overall survival with the dendritic vaccine ICT-107 in a subgroup of patients with HLA-A2+ newly diagnosed glioblastoma multiforme (GBM), warranting further exploration in a phase III study.
Patrick Y. Wen, MD
Phase II findings have shown a substantial improvement in overall survival (OS) with the dendritic vaccine ICT-107 in a subgroup of patients with HLA-A2+ newly diagnosed glioblastoma multiforme (GBM), warranting further exploration in a phase III study, according to data presented at the 2015 Society for Neuro-Oncology Annual Meeting.
The subgroup of patients showed substantial improvement in overall survival (OS) with the immunotherapy due to an immune response to ICT-107 by enzyme-linked immunospot (ELISPOT). In the group of responders from the phase II study, the median OS was 23.1 months compared with 13.7 months in non-responders (P= .0674). For responders, OS was extended by 52% compared with 29% in non-responders (P= .0615). Progression-free survival (PFS) was extended by 41% versus 15% in non-responders (P= .0259).
“ICT 107 is a dendritic cell peptide vaccine that has shown promising results in a randomized phase II study in patients with newly-diagnosed glioblastomas and was very well-tolerated,” said Patrick Y. Wen, MD, director, Center for Neuro-Oncology, Dana-Farber Cancer Institute, toldTargeted Oncology. “If the recently launched phase III study confirms these findings, it will bring a much-needed treatment to our patients.
In the study, 124 patients were randomized at a 2:1 ratio to receive ICT-107 or matching control (unincubated dendritic cells), 77% of which were HLA-A2+. Treatment arm patients (n = 81) received 4 induction doses of ICT-107 after chemoradiation, with subsequent maintenance doses until progression.
The overall median OS with ICT-107 was 18.3 versus 16.7 months for control (HR, 0.89,P= .643). Median PFS was 11.2 months with ICT-107, as opposed to 9.0 months in the control arm (HR, 0.57,P= .011). All patients in the trial received temozolomide as standard-of-care. The primary endpoint of the trial was OS with scondary endpoints being PFS along with other measures.
Limited to 7.5 months post-treatment in the HLA-A2+ group, a response measured using immune criteria to ICT-107 was found to significantly correlate with OS improvement. At this time point, the median OS with ICT-107 was 17.6 versus 13.7 months (P= .0018), with 60% of the ICT-107-treated patients demonstrating a significant immune response compared with 36% of patients in the control arm (P= 0.0084).
Furthermore, levels of IL-12 production were linked with survival. In the limited group, high IL-12 producers had a median OS of 20.6 months compared with 15.4 months for low producers (P= .0515). In the full population of HLA-A2+ responders, those who produced high levels of IL-12 had an extension in OS of 54% versus 31% in IL-12 low producers (P= .0426). In the high group, PFS was extended by 43% versus 19% in the low group (P= .0293).
“The final data from the phase II trial continue to demonstrate the therapeutic value of ICT-107 as a potential treatment for patients with newly diagnosed glioblastoma, and strongly support advancing to phase III testing,” John S. Yu, MD, founder of ImmunoCellular Therapeutics, the manufacturer of ICT-107, said in a statement.
The findings from this study help predict potential results from the larger study for ICT-107, which is composed of autologous dendritic cells incubated with 6 synthetic peptide CTL epitopes that target the GBM/stem cell-associated antigens MAGE-1, HER2, AIM-2, TRP-2, gp100, and IL-13Rα2.
The phase III registration trial will enroll more than 400 HLA-A2+ patients with GBM in approximately 120 sites in the United States, Canada, and the European Union. Patients will be randomized to received temozolomide plus control or ICT-107. The primary endpoint of the trial will be OS and secondary endpoints will be PFS and safety, as well as OS in the two pre-specified MGMT subgroups. The phase III study will employ a different control comprised of the patients’ own monocytes, which are less immunologically active than dendritic cells.
The phase III trial was formed under a special protocol assessment with the FDA, which was granted in August 2015. The study hopes to begin enrolling patients soon. Special protocol assessment is a written agreement between the sponsor company, ImmunoCellular Therapeutics, and the FDA on the design, clinical endpoints, size, and statistical design of a clinical trial. The agreement is intended support findings submitted to the FDA for regulatory filings.