TIP-19. INTERROGATE-GBM Phase I trial: Immunotherapy peptide vaccine targeting cytomegalovirus (CMV) antigens in glioblastoma

Abstract BACKGROUND Upfront standard-of-care treatment for glioblastoma (GBM) has not evolved for two decades; prognosis remains poor, particularly for patients with MGMT-unmethylated GBM who generally derive limited benefit from temozolomide (TMZ). Immunotherapies, including vaccine approaches, shows great promise in a variety of cancers, with efficacy observed even in the setting of sizeable cerebral metastases (e.g. melanoma). The discovery of CMV antigen expression in GBM, but not in the normal brain, presents a unique opportunity to harness these immunogenic viral proteins as tumour-specific targets. In an 11 GBM patients’ trial, targeting CMV antigens using at least 3 patient-derived dendritic cell vaccines resulted in a median overall survival of 41.1 months warranting further evaluation. An alternative approach using an “off-the-shelf” CMV-specific peptide vaccine (PEP-CMV vaccine) has also been tested in adult and paediatric clinical trials (PERFORMANCE and PRIME, respectively). STUDY DESIGN This is a Phase-I trial of 26 patients with newly diagnosed, MGMT-unmethylated, CMV-seropositive GBM in Australia (INTERROGATE-GBM; NCT06132438) across two treatment sites. At 4 weeks (+/-2 weeks) following standard concurrent radiotherapy and TMZ, participants receive tetanus-diphtheria booster/pre-conditioning and one cycle of adjuvant TMZ for lymphodepletion followed by PEP-CMV vaccine given fortnightly for 3 vaccines then monthly from vaccine 4 onwards, up to 12 vaccines. MRI performed every 8 weeks. Primary objectives are to evaluate feasibility and safety. Secondary objective is to quantitate specific immune responses to PEP-CMV vaccine by ELISpot. Exploratory objectives include progression-free and overall survival compared to historical controls (VERTU and PERFORMANCE), radiographic response (RANO 2.0) in patients with residual disease, and profiling of systemic and tumour-associated immune responses at progression/recurrence. PROGRESS Recruitment commenced June 2024. Up to 6 June 2025, 28 patients have been pre-screened and 12 enrolled. Among those enrolled, 5 patients have progressive disease; no patients have withdrawn from the study due to safety concerns.