NeoVax (personalized neoantigen long-peptide vaccine + poly-ICLC) plus PD-1 blockade (pembrolizumab) extends OS signals in newly diagnosed GBM

NeoVax is a personalized synthetic long-peptide neoantigen vaccine (up to 20 patient-specific peptides) formulated with the TLR3 agonist adjuvant poly-ICLC, designed to prime mutation-specific T cells; here it was combined with pembrolizumab (anti–PD-1) after gross total resection and radiotherapy in a Phase 1, four-cohort study in newly diagnosed GBM (n=39 enrolled; n=37 initiated vaccination; NCT02287428). Median OS was 36.9 months in MGMT-methylated patients and 19.0 months in MGMT-unmethylated patients, compared with 25.3 and 16.7 months in propensity score–matched historical controls, respectively; neoantigen-specific T-cell responses were seen ex vivo in 65% and in vitro in 97%, and ex vivo immune responders had better OS than non-responders (HR 0.26, 95% CI 0.09–0.77; p=0.015). Safety looked clean (no serious AEs reported), and paired tumor profiling (snRNA-seq/scTCR-seq) showed vaccine-reactive clonotypes and increased intratumoral vaccine-specific T-effector populations post-vaccination—suggesting true CNS trafficking rather than peripheral-only immunogenicity.