CTIM-08. FIRST IN HUMAN STUDY OF THE MRNA-BASED CANCER VACCINE CVGBM IN PATIENTS (PTS) WITH NEWLY-DIAGNOSED AND SURGICALLY RESECTED MGMT-UNMETHYLATED GLIOBLASTOMA (GBM): FIRST RESULTS FROM THE DOSE ESCALATION PHASE

Abstract INTRODUCTION CVGBM is an investigational therapeutic mRNA-based vaccine encoding 8 epitopes derived from tumor associated antigens with potential relevance in GBM. This is an ongoing, first-in-human study evaluating the safety of CVGBM in pts with newly-diagnosed MGMT-unmethylated GBM. METHODS HLA-A*02:01-positive pts with newly-diagnosed MGMT-unmethylated GBM (CNS WHO Grade [Gr] 4) who had a gross total or partial resection and completed radiotherapy ± concomitant temozolomide received CVGBM on Days 1, 8, 15, 29, 43, 57 and 71 + 6 optional doses at 6-week intervals. Primary endpoints are safety, tolerability and dose-limiting toxicities (DLTs). Immunogenicity is an exploratory endpoint. RESULTS As of 29/2/2024, 16 pts were enrolled in the dose-escalation part (Part A); 3 each in DL 1 (12 µg), DL 2 (25 µg), and DL 3 (50 µg), and 7 in DL 4 (100 µg). For all cohorts, mean time on study from 1st dose to last visit was 4.5 months (min: 1.5; max: 8). 109 doses were administered (mean: 6.8 doses per pt). All pts completed the 2-week DLT evaluation period without DLTs. Of 156 treatment-emergent adverse events (TEAEs), the majority (73%) were CTCAE Gr 1 (21% Gr 2, 6% Gr 3). The most common related TEAEs were chills (n=13), pyrexia (n=12), headache (n=12), fatigue (n=11) and malaise (n=5), mostly of mild to moderate severity. 7 pts had 9 ≥ Gr 3 AEs assessed as potentially related to CVGBM by the investigators outside the DLT period (cerebral edema [n=2], leukoencephalopathy, pseudoprogression with cerebral edema, structural epilepsy, ataxia, hypertension, malaise and fever [1 of each]), evenly distributed across cohorts. First immunogenicity data are planned to be presented. CONCLUSIONS CVGBM was generally well tolerated with an acceptable safety profile. The highest tolerated dose was not reached. Based on all available safety data, the selected dose for trial expansion was 100 µg. Previously presented at ESMO 2024, “FPN (Final Publication Number): 4400, Ghazaleh Tabatabai et al. - Reused with permission.