P07.02 Trials of a personalized peptide vaccine (ITK-1) for patients with recurrent or progressive glioblastoma (GBM)

Immunotherapy trials for glioblastoma (GBM) have some effects but the efficacy was limited, some because of the low immunogenicity and diverse antigens for GBMs. Personalized selection of suitable peptides for patients is one way to conquer this problem. We conducted serial series of clinical trials with 14 kinds of vaccine candidates (ITK-1) in patients with advanced cancers. Here we report our phase I results of ITK-1 in GBM and also introduce the trial design of phase III in GBM which is on-going. (Phase I) Twelve HLA-A-24 positive patients were enrolled from 8 Japanese hospitals. The dose escalation trial was conducted to determine safety and tolerability of ITK-1 peptides (at 1mg, 3mg, 5mg), however because of a dose limiting toxicity (injection site skin reaction) in another ITK-1 phase I trial for advanced prostate cancer, patients with 5mg dose was skipped or discontinued. No serious adverse drug reactions were observed. By analysis of intention to treat, two patients displayed PR, 5 SD and 5 PD by WHO criteria. The PFS rate at 6 months was 16.7%. Median OS from registration was 10.6 months. (Phase III) Based on the phase I trial, phase III trial is on-going. GBM patients refractory or recurrence after standard initial TMZ-radiation treatment were enrolled. The multi-institutional trial are conducting under IRB approval of each institutes and written informed consents from the patients and/or responsible relatives. HLA-A24 positive patients receive peptide vaccine (3mg/1.5ml) or placebo with selected 2 to 4 subcutaneous injection once weekly in total 12 times at the first course. At the second to twenty course, peptide vaccine or placebo is administered biweekly. Patients were randomly assigned (2: 1) to receive relevant peptides or placebo and both arms were under best supportive care. No other chemotherapy, immunotherapy nor radiotherapy are allowed. The primary endpoint is OS and secondary endpoints includes survival rates at 12 month, objective tumor response, immune responses and PFS. A total of 90 cases were registered and the results will be open by June 2017. So far we do not experience serious side effects, excluding one case of pulmonary embolus. Overall survival of all cases (both vaccine and placebo arms together) from registration is 8.4 months