IMMU-17. A PHASE I STUDY OF INTRATUMORAL/PERITUMORAL HERPES SIMPLEX VIRUS-1 MUTANT HSV1716 IN PATIENTS WITH REFRACTORY OF RECURRENT HIGH-GRADE GLIOMAS: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY

Abstract

Abstract BACKGROUND Immune-modulatory strategies, including checkpoint inhibition and tumor vaccines, have been tested in efforts to mitigate the pro-tumor microenvironment in pediatric high-grade glioma (pHGG). HSV1716 is a first-generation oncolytic virus that was previously reported safe with evidence of response in pediatric patients with relapsed or refractory extracranial tumors and in adults with high-grade glioma. METHODS PBTC-037 was a multicenter, phase I trial developed and performed by the Pediatric Brain Tumor Consortium (PBTC) to estimate the maximum tolerated dose or recommended phase II dose of HSV1716 administered during surgical resection. Patients aged 12 to 21 years with recurrent or refractory pHGG for whom surgical resection was clinically indicated were eligible. After maximal tumor resection, patients received one intraoperative dose of HSV1716. RESULTS Two patients were enrolled; one was later deemed ineligible (due to out-of-window screening evaluations) yet was continued in follow up for safety. Shortly after enrollment of the 2 patients, the study was closed to accrual due to a change in the sponsor’s investment focus. One patient completed the 8-week reporting period without toxicities. The only grade 3 or higher adverse event noted was grade 3 hyperglycemia at 2- and 3-months post injection. The second patient that was later deemed ineligible received the injection of HSV1716 and had no evidence of dose-limiting toxicity. The two patients had progressive disease 1.9 and 2.9 months after enrollment; both eventually died due to progressive disease at 7.5 months. CONCLUSIONS We describe the administration of HSV1716 to two pediatric patients with recurrent high-grade glioma, without evidence of dose-limiting toxicity. Oncolytic viruses are currently being tested in pediatric patients in larger trials and in combinatorial trials in other tumor types. Despite the limited numbers, the data presented here will hopefully provide incremental steps toward improved immunovirotherapy of pediatric brain tumors.