NEW clinical trial results, presented at ESMO 2024, show that an investigational mRNA-based vaccine CVGBM is safe and well-tolerated in patient with newly diagnosed MGMT-unmethylated glioblastoma (GBM). The vaccine was designed to target eight tumour-associated antigens relevant to GBM and was tested in a first-in-human study focusing on safety, tolerability, and dose-limiting toxicities (DLT’s).
The trial enrolled 16 HLA-A*02:01-positive patients with newly diagnosed MGMT-unmethylated GBM who had undergone partial or total tumour resection and completed radiotherapy combined with temozolomide. The patients received CVGBM at increasing dose levels of 12, 25, 50, and 100mg over a schedule that included multiple initial doses and optional follow-ups. The primary endpoints of the study were safety and tolerability, with immunogenicity as an exploratory endpoint. This first phase of the study included a dose-escalation component, with plans to further expand dosing in the second phase of the study.
As of February 2024, participants had received a total of 109 doses of CVGBM, averaging 6.8 doses per patient over approximately 4.5 months. Importantly, no DLTs were observed during the two-week evaluation period for any dose level. The study reported that among the 156 treatment-emergent adverse events (TEAEs) most were mild to moderate with only 6% of TEAEs reported at Grade 3, and seven patients experienced severe adverse events, such as cerebral oedema, and structural epilepsy, which were assessed as potentially related to the vaccine but were not dose-limiting.
The findings show that CVGBM was generally well-tolerated across all dose levels, with no maximum tolerated dose reached. Based on these safety findings, the study will proceed with a 100mg dose in the expansion phase of the trial.
These initial results are promising, indicating that CVGBM may offer a new therapeutic option for patients with aggressive brain cancer. The researchers plan to gather more data on immunogenicity outcomes that could offer more insights into the vaccine’s potential effectiveness against GBM.
Aleksandra Zurowska, EMJ
Reference
Tabatabai G et al. 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 4400. ESMO Annual Meeting, 13-17 September, 2024.
