Abstract
The IMA950 peptide vaccine is composed of 9 HLA-A2-restricted peptides eluted from the surface of GBM samples and of two HLA class II-binding peptides1. It was tested in combination with poly-ICLC in patients with newly diagnosed GBM, demonstrating safety. The vaccine was able to elicit CD4 and CD8 T cell responses in the peripheral blood in the majority of patients, with however an overall low magnitude of T cell responses and suboptimal migration of elicited T cells to the brain, probably limiting clinical efficacy2,3. With the aim to improve homing of vaccine-specific T cell to the tumor, we are conducting a phase II clinical trial in patients with recurrent GBM testing the IMA950/poly-ICLC multipeptide vaccine with or without the anti-PD1 antibody pembrolizumab (NCT03665545). 24 patients will be included (12 patients in each arm) and pre- and post-vaccination tumor sample will be available, allowing assessing effect of the vaccine at the tumor site. The primary objective of this trial is safety of IMA950/poly-ICLC given together with pembrolizumab. Secondary objectives include (i) estimation of 6, 9 and 12-month progression-free survival (PFS), (ii) overall survival, (iii) analysis of patient quality of life and (iv) of the synergy/immunogenicity of IMA950/poly-ICLC and pembrolizumab. Immunomonitoring will include measure of vaccine-induced immune responses, IHC for immune cell markers, RNA/TCR sequencing and methylome analysis, to assess vaccine-induced T cell responses, immune modulation and potential signatures predictive of response. Thus far, 6 patients have been included (3 in each arm). Preliminary results show CD4 and CD8 T cell responses to the vaccine are detected in both groups in the peripheral blood. Analysis at the tumor site and comparison between arms will be performed once all patients have been included. 1. Dutoit, V. et al. Brain (2012); 2. Migliorini, D. et al. Neuro Oncol (2019); 3. Rampling, R. et al. Clin Cancer Res(2016)
The Breadth of Synthetic Long Peptide Vaccine-Induced CD8+ T Cell Responses Determines the Efficacy against Mouse Cytomegalovirus Infection