CTIM-15. EO2401 PEPTIDE IMMUNOTHERAPY + NIVOLUMAB +/- BEVACIZUMAB IN FIRST RECURRENT GLIOBLASTOMA: TREATMENT STRATEGY OPTIMIZATION IN THE PHASE 1/2 STUDY EOGBM1-18 / ROSALIE (NCT04116658)

Abstract EO2401, composed of peptide sequences from gut bacteria that cross-react with glioblastoma tumor-associated antigens (IL13Rα2, BIRC5/survivin, and FOXM1) plus a helper peptide, was administered to HLA-A2 positive patients with first progression of a glioblastoma requiring ≤ 2 mg dexamethasone/day. Mature data from cohorts-2a/2b (EO2401/nivolumab, n=44) and 3 (EO2401/nivolumab/bevacizumab, n=26) are provided. Ex vivo tetramer-staining on PBMCs demonstrated expansion of CD8 T-cells specific for EO2401 TAAs in 84% of tested patients for cohort-2a/2b and in 92% for cohort-3. Adverse events were limited to those expected for nivolumab and bevacizumab, as well as local site reactions to EO2401 (96% events grade 1-2). Improved outcomes were observed for cohort-3 (median follow-up 33.5 months) versus 2a/2b (median follow-up 25.0 months) including: time of study therapy (4.8 vs 2.3 months), median PFS (4.8 vs 1.9 months), ORR (38% vs 14%) and median OS (12.1 vs 10.8 months). Median OS for patients who underwent second surgery prior to EO2401 start vs no surgery were 18.5 vs 8.5 months for cohort-3 and 11.1 vs 10.2 months for cohort-2a/2b. Multivariable Cox regression analyses revealed that OS for cohort-3, but not cohort 2a/2b was associated with second surgery (HR=0.08, 95%-CI 0.01–0.75, p=0.027), gender (HR=10.2, 95% CI 2.17–48.3, p=0.003) and baseline dexamethasone use (HR=9.35, 95%-CI 2.03–43.1, p=0.004) whereas MGMT methylation status and tumor size was not. For external validation, application of the same model to the CM-143 dataset (1st glioblastoma progression randomized to nivolumab [n=83] vs bevacizumab [n=77]) revealed no associations with OS for bevacizumab while MGMT status (HR=1.95, 95%-CI 1.12–3.17, p=0.007) and baseline corticosteroid use (HR=2.30, 95%-CI 1.42–3.71, p=0.001) associated with OS for nivolumab. Our data indicate that a randomized trial further evaluating EO2401 is warranted and also suggest that surgery prior to triplet therapy, along with baseline dexamethasone use, should be further investigated.