Todo 2022: the triple-mutated herpes virus that became Japan's first approved oncolytic virus

Investigator-initiated, single-arm phase 2 trial of G47 delta, a triple-mutated third-generation oncolytic herpes simplex virus type 1, in 19 adults with residual or recurrent supratentorial glioblastoma after radiotherapy and temozolomide. The virus was given into the tumour, repeatedly, for up to six doses.

The primary endpoint, one-year survival after starting G47 delta, was 84.2 per cent (95% CI 60.4 to 96.6; 16 of 19). The prespecified endpoint was met and the trial stopped early. Median overall survival was 20.2 months from starting G47 delta and 28.8 months from the initial surgery. Fever was the commonest related adverse event, in 17 of 19. Imaging repeatedly showed the target lesion enlarging with clearing of contrast enhancement after each dose, a pattern characteristic of this therapy, so the best overall response over two years was partial response in one patient and stable disease in 18. Biopsies showed increasing tumour-infiltrating CD4-positive and CD8-positive lymphocytes with persistently low Foxp3-positive cells. The result led to approval of G47 delta in Japan.