Evaluation of GM-CSF and AS01B adjuvants in a phase I/IIa trial of a therapeutic CMV vaccine (VBI-1901) against recurrent glioblastoma (GBM).

Abstract

2047 Background: Cytomegalovirus (CMV) antigens have been reported in over 90% of GBMs. CD4+ and CD8+ T cells are most frequently directed against the gB and pp65 antigens, respectively, and are immunogenic targets in a CMV-based GBM vaccine. Methods: We enrolled a total of 20 patients with KPS at least 70 and first recurrence of GBM into 2 arms of the Phase IIa extension of gB/pp65 enveloped virus-like particles (eVLPs) adjuvanted with either GM-CSF given intradermally or with AS01B given intramuscularly (NCT03382977). Patients were vaccinated with VBI-1901 every 4 weeks, with serologic immune-monitoring 2 weeks after each vaccination and surveillance brain MRI scans every 6 weeks. Results: 10 patients (6 women, 4 men) with a median age of 58 (33-67 yrs) were enrolled into the GM-CSF arm and 10 patients (3 women, 7 men) with a median age of 65 (40-67) enrolled into the AS01B arm. Disease control rates of 40% and 50% were observed in the GM-CSF and AS01B arms, respectively, with 2 sustained PRs in the GM-CSF arm. The 6-month OS rate for the GM-CSF arm is 80% and is estimated to be comparable for the AS01B arm. CMV-specific CD4+ effector memory T cells may correlate with tumor responses in both arms of the study, with AS01B boosting higher frequencies of these cells regardless of baseline CD4/CD8 ratio. Conclusions: These encouraging results from both arms of the trial justify further clinical evaluation in a randomized, controlled trial expected to begin later in 2021. Clinical trial information: NCT03382977.