Multicenter phase 1-2 trial of oncolytic DNX-2401 virotherapy plus pembrolizumab for recurrent glioblastoma

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. A phase 1-2 trial at 13 centers in Canada and the United States evaluated the combination of intratumoral delivery of oncolytic virus DNA-2401 followed by intravenous pembrolizumab (anti-PD-1). The primary safety end point was met. There were no dose-limiting toxicities, and full dose treatment was well tolerated. The objective response rate was 10.4% (90% CI 4.2-20.7), which was not statistically greater than the prespecified control rate of 5%. More than half of patients had clinical benefit. The secondary endpoint of overall survival rate at 12 months was 52.7% (95% CI 40.1-69.2), which was statistically greater than the prespecified control rate of 20%. The authors conclude that the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients with recurrent glioblastoma.