283 Phase I Clinical Trial of M032, an IL-12 Expressing Oncolytic HSV-1, for Adult Patients With Recurrent Malignant Glioma

INTRODUCTION: Effective treatment options are limited for patients diagnosed with malignant glioma, and outcomes remain very poor. Recurrence and progression rates are universal. Preclinical data showed that a second-generation oncolytic herpes virus (oHSV) with selective replication and armed to induce IL-12 expression was a more effective anti-glioma agent than the first-generation oHSV. METHODS: We conducted an open-label, dose-escalating phase I trial to determine the safety and tolerability of intratumoral injection of the M032 virus in patients with recurrent or progressive MG. Patients underwent stereotactic placement intratumoral catheters. The following day, M032 was infused over a period of 6 hours. Primary endpoint was to determine safety and maximum tolerated dose (maximal planned dose of 109 PFU). Dose elevations were made using a modified Continual Reassessment Method. RESULTS: Twenty-one patients with recurrent MG ages 19 to 71 received M032 (16 Males, 5 Females). Fourteen patients had IDH wild-type tumors, and eighteen had unmethylated MGMT status. Four grade 1, two grade 2, two grade 3, and two grade 4 adverse events were identified as possibly associated with M032. Both grade 3 and grade 4 adverse events possibly associated with M032 occurred in a single patient on the 108 PFU cohort. No serious adverse events at the maximally plan dose were attributed to M032. Median post-treatment survival was 9.38 months (95% CI, 7.57 to 12.95). 2 participants were still alive following treatment. CONCLUSIONS: Intratumoral M032 had an acceptable adverse-event profile. We observed two grade 3 and two grade 4 adverse events in a patient with a large tumor prompting an amendment to tumor size inclusion criteria. No dose-limiting toxicity occurred at maximum dose. Preliminary evidence suggests favorable response in some patients with recurrent or progressive MG. Careful selection of patients is needed when considering treatment with M032 (ClinicalTrials.gov number, NCT02062827).