Evaluation of tumor responses and overall survival in patients with recurrent glioblastoma (GBM) from a phase IIa trial of a CMV vaccine immunotherapeutic candidate (VBI-1901).

Abstract

2014 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, which are immunogenic targets in a CMV-based GBM immunotherapeutic. Methods: A total of 20 first-recurrent GBM patients were enrolled, with Karnofsky Performance Status of at least 70, across 2 arms of the Phase IIa extension phase to receive VBI-1901 (a gB/pp65 enveloped virus-like particle [eVLP]) adjuvanted with either GM-CSF (given intradermally) or 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. The 12-month OS rates for the GM-CSF and AS01B arms were 60% and 70%, respectively; the 18-month OS rate for the GM-CSF arm was 30%, and for the AS01B arm is expected to be 30%-40% (data has not yet matured). Two durable partial responses (locally determined by RANO) have been observed in the GM-CSF arm, with one patient progression-free and on protocol after 2 years with a tumor size reduction of 93% relative to start of treatment. Immunological analyses demonstrate that prolonged, monthly dosing with VBI-1901 does not lead to immunological tolerance. Dynamic boosting and loss in the peripheral blood of CMV-specific CD4 Tem cells after treatment with VBI-1901 formulated with GM-CSF may correlate with tumor responses. Conclusions: The U.S. FDA granted Fast Track Designation to VBI-1901 adjuvanted with GM-CSF in first-recurrent GBM patients, and an expansion of the ongoing trial with this formulation in this patient population, with the addition of randomization with a contemporaneous control arm, is anticipated to begin in H1 2022. Acknowledgement: GlaxoSmithKline Biologicals SA provided the AS01B adjuvant used in this study. Clinical trial information: NCT03382977.