Non-secreting IL12 expressing oncolytic adenovirus Ad-TD-nsIL12 in recurrent high-grade glioma: a phase I trial.

Malignant glioma is a highly fatal central nervous system malignancy with high recurrence rates. Oncolytic viruses offer potential treatment but need improvement in efficacy and safety. Here we describe a phase I, dose-escalating, single arm trial (ChiCTR2000032402) to study the safety of Ad-TD-nsIL12, an oncolytic adenovirus expressing non-secreting interleukin-12, in patients with recurrent high-grade glioma that connects with the ventricular system. Eight patients received intratumoral treatment via stereotaxis or an Ommaya reservoir, with doses ranging from 5 × 10 to 5 × 10vp. The primary end point was to determine the maximal tolerated dose. Secondary endpoints included toxicity and anti-tumour ability. Minimal adverse events were observed at doses of 5 × 10 and 1 × 10vp. Grade 3 seizure was observed in two patients from Cohort 3 (5 × 10vp). Therefore, the maximum tolerated dose was determined to be 1 × 10vp. Four patients developed hydrocephalus during follow-up. Among them, symptoms in two patients were relieved after placement of a ventriculo-peritoneal shunt, and the other two only showed ventriculomegaly on MRI scan without neurological deterioration. Complete response (according to Response Assessment in Neuro-Oncology Criteria) in one patient, a partial response in one patient and post-treatment infiltrations of CD4+ and CD8 + T cells into the tumour were documented during this trial. In conclusion, Ad-TD-nsIL12 has demonstrated safety and preliminary efficacy in patients with recurrent high-grade glioma.