BIOM-04. Immune correlates from a Phase 1 trial of a peptide vaccine targeting CMV antigen pp65 in children and young adults with recurrent high-grade glioma

Introduction We recently completed a Phase I trial (NCT03299309) of a novel peptide vaccine targeting pp65 (PEP-CMV) in children/young adults with recurrent high-grade glioma. PEP-CMV was admixed with Montanide ISA51 and delivered intradermally every 2 weeks for 3 doses, then monthly. Methods ELISpot was used to assess antigen-specific immune response. Peripheral blood mononuclear cell types/phenotypes and HLA-A2 type were determined using flow cytometry. Multiplexed cytokine profiling of T cells was completed in select patients representing short, median, and long overall survival (OS). Results Complete immune analyses (received ≥3 vaccines) were available for the 21 patients. CMV seropositive patients (n = 12) had significantly increased median IFN-γ spots compared to CMV seronegative (n = 9) patients at baseline (16 vs 0, P = 0.002) and vaccine #4 timepoints (162 vs 4, P = 0.009). The median overall survival (OS) of CMV seronegative patients was 8.6 months (95% CI 5.1, 29.7) and the median OS of CMV seropositive patients was 12.6 months (95% CI 3.4, 17.6, P = 0.73). Increased pretreatment regulatory T cell percent was associated with shorter PFS (HR 1·79 [95%CI 1·03, 3·11]). Naïve CD8+ T cells above the cohort median was associated with more favorable PFS than those with counts below the median (P = 0.0055). Ratio of CD56brightCD16dim NK cells compared to baseline were predictive of OS (HR 1.74 [95%CI 1.01,3] P = 0.047) but not PFS (HR 1.23, [95%CI 0.86,1.76], P = 0.3). Increased T cell polyfunctionality as specified by INF-γ, TNF-α, and IL-2 phenotype, corresponded with increased number of vaccines received. HLA-A2 status was not significantly associated with PFS (P = 0.34) nor OS (P = 0.86). Conclusions Neither CMV or HLA-A2 status was associated with survival in this heavily pretreated cohort. CMV seropositive patients had a significantly higher antigen-specific T cell responses. Higher percentage of baseline regulatory T cells was associated with worse PFS while higher ratio CD56brightCD16dim NK cells was associated with worse OS.