PDCT-17 (LTBK-11). PNOC007: H3.3K27M SPECIFIC PEPTIDE VACCINE COMBINED WITH POLY-ICLC FOR THE TREATMENT OF NEWLY DIAGNOSED HLA-A2+ H3.3K27M MIDLINE GLIOMAS

Abstract

OBJECTIVE: To assess within a multi-center trial the safety of H3.3K27M specific peptide vaccine in combination with poly-ICLC in HLA-A02.01+ patients diagnosed with H3.3K27M+ diffuse midline gliomas. METHOD(S): Subjects 3-21 years of age with CLIA confirmed H3.3K27 mutation status were eligible. Patients were enrolled after completion of focal radiation therapy. The trial enrolled two strata: Stratum A included newly diagnosed patients with diffuse intrinsic pontine glioma (DIPG) (n=19); Stratum B included non-DIPG midline glioma patients including spinal cord tumors as an exploratory strata (n=10). The H3.3K27M vaccine was administered in combination with poly-ICLC every 3 weeks for a total of 8 doses followed by every 6 weeks for a maximum of 96 weeks of therapy. Immuno-monitoring and imaging occurred every 3 months. Modi- fied iRANO criteria are used for ongoing assessment of disease status. Patients' peripheral blood mononuclear cell (PBMC) samples were evaluated by mass cytometry. RESULT(S): From November 2016 until March 2019, 19 eligible patients (median age 11, range 5-17 yrs; 53 % female) were enrolled in Stratum A and 10 eligible patients (median age 13, range 7-18 yrs; 60 % female) in Stratum B. Treatment was well tolerated with 7 grade 3 and 0 grade 4 treatment related toxicities. The most common related side effect included injection site reaction. Median number of vaccine administrations per patient was 6 (range 1-11). Overall survival at 12 months was 40% (95% CI 22-73%) for Stratum A and 39% (95% CI 16-93%) for Stratum B. A mass cytometry-based analysis of patient PBMCs (n = 16) revealed a trend towards an inverse correlation between polymorphonuclear myeloid-derived suppressor cells and the expansion of H3.3K27M-specific CD8+ T-cells (p-value = 0.154). CONCLUSION(S): H3.3K27M specific vaccine in combination with poly-ICLC is well tolerated. Further evaluation will include a combination with checkpoint inhibitor nivolumab.