ON-01, an engineered recombinant oncolytic herpes simplex virus type-1, in recurrent glioma: a single-arm, phase 1/2 study
Mené sur 30 patients atteints d'un gliome récidivant et de grade 4 selon la classification de l'OMS (43 % d'hommes ; âge médian : 50 ans), cet essai de phase I/II évalue la sécurité d'une injection intratumorale de ON-01, un virus herpès simplex de type 1 recombinant oncolytique
The prognosis of patients with recurrent WHO grade 4 glioma is poor, particularly in glioblastoma (GBM), which has a median survival of approximately 6 months and no effective treatment options. We evaluated the short-term (28-day) safety and efficacy of ON-01, an engineered recombinant oncolytic herpes simplex virus type-1, in patients with recurrent WHO grade 4 glioma.In this single-arm, phase 1/2 clinical trial, eligible patients received intratumoral injections of ON-01 under stereotactic guidance. The primary endpoint was to assess the short-term safety profile of ON-01 treatment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the 2-year OS rate. An exploratory objective was to identify tumor-related biomarkers predictive of treatment efficacy.Of the 30 patients treated with ON-01, 13 (43.3%) were male, and the median age was 50.0 years (range, 22–75). A total of 36 grade 1, 12 grade 2, and 2 grade 3 adverse events were reported. Among all treated patients, the median OS was 12.0 months (95% CI, 10.1–13.9), median PFS was 3.0 months (95% CI, 1.7–4.3), and 2-year OS rate was 27.7% (95% CI, 12.6%–45.0%). Seven patients with recurrent multifocal gliomas demonstrated regression of non-injection site lesions following ON-01 therapy. Furthermore, patients with elevated expression of herpesvirus entry mediator exhibited significantly prolonged survival (p=0.015).Intratumoral infusion of ON-01 appeared safe and demonstrated efficacy in patients with recurrent malignant glioma, with no evidence of neurotoxicity. The therapeutic response to ON-01 may be associated with HVEM expression levels.
Neuro-Oncology , article en libre accès, 2026