IMA950 multipeptide vaccine adjuvanted with poly-ICLC in combination with standard therapy in newly diagnosed HLA-A2 glioblastoma patients

Abstract

Background: Immunotherapy is a promising alternative strategy for patients with glioblastoma (GBM). Here, we conducted a phase I/II trial to address the safety and immunogenicity of a multipeptide therapeutic vaccine (IMA950) adjuvanted with Poly-ICLC in patients with newly diagnosed GBM. Method(s): Sixteen HLA-A2+ GBM patients were included. Patients received the standard of care treatment including surgery, 6-week chemo-radiation therapy, and 6-12 adjuvant cycles of temozolomide. IMA950 (composed of nine glioma-Associated CD8 peptides and two tumor-Associated CD4 peptides) was injected starting one week after the end of chemo-radiation therapy. Primary endpoints were safety and immunogenicity; secondary endpoints were OS and PFS at six and nine months. Result(s): In the first six patients, peptides were injected intradermally (i.d.) and Poly- ICLC intramuscularly (i.m.). Low levels of vaccine-induced CD8 T cell responses were detected following this vaccination schedule, leading us to modify the vaccination protocol. In the modified schedule, peptides and adjuvant were mixed before injection, which was given i.m. for six patients and subcutaneously (s.c.) for seven patients, in an effort to determine the optimal injection route. Clinically, the IMA950/Poly-ICLC vaccine was well tolerated, the most common side effect being local inflammation at the injection site. A few patients experienced cerebral edema, which was manageable with steroids. Analysis of vaccine-induced T cell responses revealed that 63% of patients responded to one CD8 peptide and 37% responded to two or more CD8 peptides. Modifying the vaccination protocol resulted in detection of multipeptide responses in 46% of patients, as compared with 17% in the initial protocol. Vaccine-induced CD4 T cell responses were detected in the majority of patients and were of Th1 phenotype. Median OS was 21.2 months. Conclusion(s): Overall, the IMA950/Poly-ICLC vaccine is safe, immunogenic and preliminary median OS is encouraging. Definitive clinical results and correlation with immunological data will indicate the most efficacious route of vaccination for use in further trials in glioma patients.