日本东京大学Tomoki Todo等研究人员完成瘤内溶瘤疱疹病毒G47?治疗残留或复发胶质母细胞瘤的2期临床试验。2022年7月21日，《自然—医学》杂志在线发表了这项成果。

Author: Todo, Tomoki, Ito, Hirotaka, Ino, Yasushi, Ohtsu, Hiroshi, Ota, Yasunori, Shibahara, Junji, Tanaka, Minoru

Issue&Volume: 2022-07-21

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 2yr 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.

DOI: 10.1038/s41591-022-01897-x

Source: https://www.nature.com/articles/s41591-022-01897-x