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.

这项由研究人员发起的 2 期单臂试验主要评估了 G47Δ（一种三突变的第三代溶瘤单纯疱疹病毒 1 型）在 19 名接受放疗后残留或复发的幕上胶质母细胞瘤成人患者中的疗效，以及替莫唑胺（UMIN-CTR 临床试验注册中心 UMIN000015995）。G47Δ 瘤内反复给药最多六剂。G47Δ 启动后 1 年生存率的主要终点为 84.2%（95% 置信区间，60.4-96.6；19 个中的 16 个）。达到了预先设定的终点，试验提前终止。关于次要终点，中位总生存期为 G47Δ 开始后 20.2（16.8-23.6）个月和初次手术后 28.8（20.1-37.5）个月。最常见的 G47Δ 相关不良事件是发烧（19 个中的 17 个），其次是呕吐、恶心、淋巴细胞减少症和白细胞减少症。在磁共振成像上，每次 G47Δ 给药后靶病灶内的扩大和对比增强清除反复发生，这是该疗法的特征。因此，2 年内最好的总体反应是 1 名患者的部分反应和 18 名患者的疾病稳定。活检显示肿瘤浸润性 CD4 数量增加⁺ /CD8 ⁺淋巴细胞和持续少量的 Foxp3 ⁺细胞。该研究显示了生存益处和良好的安全性，这导致 G47Δ 被批准为日本第一个溶瘤病毒产品。