Todo et al. conducted a single-arm, phase II trial of a mutated oncolytic herpes virus (G47Δ) administered intratumorally in glioblastoma that recurred or was incompletely resected. Adverse events were primarily immune-related, likely in response to the viral load. Although radiographic responses were limited, the overall 1-year survival in 13 patients at 12 months was 92%, prompting early termination of the trial and regulatory approval of the product in Japan. The 1-year survival was 84% in the 19 patients in the full analysis set; median OS was nearly 29 months. Neither IDH1 nor MGMT status affected outcomes (post-hoc), and TILs increased with dosing and persisted.
Contributed by Ed Fritsch
ABSTRACT: This investigator-initiated, phase 2, single-arm trial primarily assessed the efficacy of G47∆, a triple-mutated, third-generation oncolytic herpes simplex virus type 1, in 19 adult patients with residual or recurrent, supratentorial glioblastoma after radiation therapy and temozolomide (UMIN-CTR Clinical Trial Registry UMIN000015995). G47Δ was administered intratumorally and repeatedly for up to six doses. The primary endpoint of 1-yr survival rate after G47∆ initiation was 84.2% (95% confidence interval, 60.4-96.6; 16 of 19). The prespecified endpoint was met and the trial was terminated early. Regarding secondary endpoints, the median overall survival was 20.2 (16.8-23.6) months after G47∆ initiation and 28.8 (20.1-37.5) months from the initial surgery. The most common G47∆-related adverse event was fever (17 of 19) followed by vomiting, nausea, lymphocytopenia and leukopenia. On magnetic resonance imaging, enlargement of and contrast-enhancement clearing within the target lesion repeatedly occurred after each G47∆ administration, which was characteristic to this therapy. Thus, the best overall response in 2 yr was partial response in one patient and stable disease in 18 patients. Biopsies revealed increasing numbers of tumor-infiltrating CD4+/CD8+ lymphocytes and persistent low numbers of Foxp3+ cells. This study showed a survival benefit and good safety profile, which led to the approval of G47∆ as the first oncolytic virus product in Japan.