ONYX-015 is an oncolytic virus untested as a treatment for malignant glioma. The NABTT CNS Consortium conducted a dose-escalation trial of intracerebral injections of ONYX-015. Cohorts of six patients at each dose level received doses of vector from 107 plaque-forming units (pfu) to 1010 pfu into a total of 10 sites within the resected glioma cavity. Adverse events were identified on physical exams and testing of hematologic, renal, and liver functions. Efficacy data were obtained from serial MRI scans. None of the 24 patients experienced serious adverse events related to ONYX-015. The maximum tolerated dose was not reached at 1010 pfu. The median time to progression after treatment with ONYX-015 was 46 days (range 13 to 452 + days). The median survival time was 6.2 months (range 1.3 to 28.0 + months). One patient has not progressed and 1 patient showed regression of interval-increased enhancement. With more than 19 months of follow-up, 1/6 recipients at a dose of 109 and 2/6 at a dose of 1010 pfu remain alive. In 2 patients who underwent a second resection 3 months after ONYX-015 injection, a lymphocytic and plasmacytoid cell infiltrate was observed. Injection of ONYX-015 into glioma cavities is well tolerated at doses up to 1010 pfu. Copyright © The American Society of Gene Therapy.