ATIM-21. IMA950 PEPTIDE-BASED VACCINE ADJUVANTED WITH POLY-ICLC IN COMBINATION WITH STANDARD THERAPY IN NEWLY DIAGNOSED HLA-A2 GLIOBLASTOMA PATIENTS: PRELIMINARY RESULTS

Abstract

Phase I/II trial: HLA-A2 positive newly diagnosed GBM patients received after surgery, standard concurrent chemoradiation with temozolomide. In addition patients underwent 6 (before protocol amendment) or 4 (after protocol amendment) vaccinations of IMA-950 with poly ICLC (TLR3 agonist) once a week starting one week after the end of radiation, then 5 vaccinations once a month alternately with the 6 cycles of temozolomide. Primary endpoint was safety, secondary were OS, PFS at 6, 9 months, and immunological endpoints. 19 patients have been enrolled. The first 6 patients received the vaccine intradermally and the adjuvant intramuscularly (IM) in close vicinity and the site varied to stimulate the major draining lymph nodes. The preliminary analysis of vaccine-induced T cell responses didn't show any induction of peptide-specific CD4 or CD8 T cells, leading to design a novel vaccination schedule/formulation. An amendment in the protocol incorporated the following changes: mixing vaccine/adjuvant before injection at one single site (thigh), decreasing the number of vaccinations during the induction phase, testing two different injection routes for the remaining 13 patients (subcutaneously or IM). Clinically, IMA-950 was well tolerated, the most common side effect was local inflammatory reaction at the injection site with mild fever. Some patients experienced cerebral edema, manageable with steroids. Among the 6 first patients, 2 showed disease progression, and median OS was 17.5 months (11-21). Patients under the amended protocol are still under therapy for 3 of them and 5 others finished the study protocol and are being followed without tumor recurrence. Analysis of vaccine-induced T cell responses in two of the 13 amended patients showed induction of both peptide-specific CD4 and CD8 T cells, suggesting those changes might lead to better immunization. IMA- 950 is safe, preliminary mOS seems to be improved. Objective immune responses in two patients were observed.