Neurosurgery University of Toronto Toronto, Ontario, Canada
Disclosure(s):
Farshad Nassiri, MD, PhD: No financial relationships to disclose
Introduction: Recurrent glioblastoma is a rapidly fatal disease for which there are no effective treatment options. Oncolytic viral therapies directly kill cancer cells and elicit immune-mediated anti-tumoral responses that may be augmented with checkpoint inhibition.
Methods: This multicenter, phase 1/2 study assessed the safety and efficacy of single intratumoral dose of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody, pembrolizumab, every 3 weeks, first in a dose-escalation phase and then in a dose-expansion phase in patients with recurrent glioblastoma (ClinicalTrials.gov: NCT02798406).
Results: A total of 49 patients were enrolled. There were no dose limiting toxicities and 5x1010 vp DNX-2401 plus pembrolizumab was identified as the declared dose for the dose expansion phase. Adverse events were well tolerated with brain edema and headache being cost common. There were no deaths related to adverse events from treatment. The objective response rate was 11.9% (90% confidence interval [CI] 4.8 to 23.4). A total of 54.8% of patients (95%CI 38.7 to 70.2) had a clinical benefit defined as stable disease or better. Overall survival at 12 months was 53.1% (95%CI 36.8 to 67.0) and this was greater than the prespecified rate of 20%. The median overall survival was 12.5 months (95%CI 10.2 to 13.0). Patients with objective responses had longer survival than patients without objective responses (Hazard Ratio 0.20, 95%CI 0.03 to 0.36, p=0.018). Three patients completed pembrolizumab treatment with durable responses and remain alive at 39 and 42 months. Objective responses were enriched for patients with a moderately inflamed microenvironment and elevated PD-1.
Conclusion : Overall, intratumoral delivery of 5x1010 vp DNX-2401 followed by pembrolizumab was safe with notable objective responses and survival benefit in patients with recurrent glioblastoma.
