A phase I trial investigating the clinical safety and anti-tumor efficacy of a new generation of oncolytic adenovirus, Ad-TD-nsIL12, in Recurrent Glioblastoma

Abstract Glioblastoma is one of the most fatal malignancies of the central nervous system, with high mortality and post-treatment recurrence rates. Oncolytic viruses are attractive treatment options for this disease, but must be improved to enhance efficacy and safety. Here we describe a phase I, dose-escalating trial to study the safety of Ad-TD-nsIL12, a novel oncolytic adenovirus expressing a mutant form of interleukin-12, in patients with recurrent glioblastoma that connects with the ventricular system. Eight patients, were enrolled, with treatment doses ranging from 5x109vp to 5x1010vp. Grade 3 seizure was observed in two patients from Cohort 3 (5x1010vp). Minimal adverse events were observed at a treatment dose of 1x1010vp, even after multiple injections. Complete response in one patient, a partial response in one patient and post-treatment infiltrations of CD3+, CD4+ and CD8+ T cells into the tumor were documented during this trial. AD-TD-nsIL12 treatment was safe and effective and warrants examination in a phase II clinical study.