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.
Author Info: (1) Division of Innovative Cancer Therapy, Advanced Clinical Research Center, and Department of Surgical Neuro-Oncology, The Institute of Medical Science, The University of Tokyo,
Author Info: (1) Division of Innovative Cancer Therapy, Advanced Clinical Research Center, and Department of Surgical Neuro-Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. toudou-nsu@umin.ac.jp. (2) Division of Innovative Cancer Therapy, Advanced Clinical Research Center, and Department of Surgical Neuro-Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. (3) Division of Innovative Cancer Therapy, Advanced Clinical Research Center, and Department of Surgical Neuro-Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. (4) Department of Data Science, National Center for Global Health and Medicine in Japan, Tokyo, Japan. Leading Center for the Development and Research of Cancer Medicine, Juntendo University, Tokyo, Japan. (5) Department of Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. (6) Department of Pathology, Kyorin University School of Medicine, Tokyo, Japan. (7) Division of Innovative Cancer Therapy, Advanced Clinical Research Center, and Department of Surgical Neuro-Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
