Phase 1 dose-finding study to evaluate safety and tolerability of CVGBM in patients with newly diagnosed and surgically resected MGMT-unmethylated glioblastoma.

• DOI: 10.1200/jco.2024.42.16_suppl.tps2095
• Publication Date: 2024-07-11T20:25:19Z
• Authors: Ghazaleh Tabatabai; Louisa Von Baumga...; Martin J. Van Den...; Michael C Burger; Pierre Freres; Martin Glas; Peter Hau; Ulrich Herrlinger; Iris Mildenberger; Bart Neyns; Henning Sebastian...; Clemens Seidel; Rachel Galot; Antje Wick; Martin H. Falk; Laura Leticia de ...; Peter Kelemen; Sven D Koch; Paula Romer Roche; Senta Ulrike Gnad...
• Keywords: Tolerability

TPS2095 Background: Glioblastoma (GBM) is characterized by a low mutational burden limiting the number of neoantigen targets for cancer vaccines. Vaccination against tumor-associated antigens over-presented via MHC class I and II in GBM an alternative that has shown promise previous trials. A vaccine containing peptides presented HLA-A*02:01 (class I) some DR alleles II), showed evidence peripheral intratumoral vaccine-induced immune response these patients with GBM. Our study will assess safety immunogenicity messenger ribonucleic acid (mRNA)-based multiepitope CVGBM, investigational therapeutic mRNA vaccine, encoding eight have demonstrated as peptide CVGBM consists unmodified nucleotides formulated lipid nanoparticles. Methods: CV-GBLM-001 (NCT05938387) first-in-human, open-label, international, dose-escalation phase 1 trial. HLA-A*02:01-positive newly diagnosed MGMT-unmethylated (CNS WHO Grade 4), including IDH-wildtype astrocytoma molecular signature unmethylated glioblastoma who had gross total or partial resection completed post-surgery radiotherapy without chemotherapy, are eligible to receive CVGBM. The trial comprises part (Part A) followed dose-expansion B). In Part A, dose levels between 12 100 µg being investigated escalation guided Bayesian logistic regression model. Patients 7 doses intramuscular injection on Days 1, 8, 15, 29, 43, 57, 71, 6 optional at 6-week intervals, up year after first until disease progression intolerable toxicity. An independent Data Safety Monitoring Board recommend expansion B about 20 be enrolled. Biomarkers innate adaptive immunogenicity, including, but not limited to, systemically induced cytokines chemokines antigen-specific CD4 + CD8 T cells, monitored blood, optionally vaccine-draining lymph nodes progressive tumors. addition primary objectives, secondary objectives efficacy (progression-free survival, overall survival) patient-reported quality life outcomes assessed. Trial sponsor: CureVac SE, Germany. Clinical information: NCT05938387 .