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

Source: https://onco.cc/key-papers/paper-todo-g47delta-glioblastoma-natmed-2022/  
OnCo record `paper-todo-g47delta-glioblastoma-natmed-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Nineteen people with a brain tumour that had come back after radiotherapy and chemotherapy were given repeated injections of an engineered herpes virus, and more of them were alive at one year than expected.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Nature Medicine
- Year: 2022
- DOI: 10.1038/s41591-022-01897-x
- Authors: Todo T, Ito H, Ino Y, et al.
- Findings: One-year survival after starting G47 delta was 84.2 per cent (95% CI 60.4 to 96.6), 16 of 19 patients; the prespecified endpoint was met and the trial ended early.; Median overall survival 20.2 months from starting treatment and 28.8 months from the initial surgery.; Best overall response over two years was partial response in one patient and stable disease in 18; the tumour typically enlarged on imaging after each dose while contrast enhancement cleared.; Fever was the commonest related adverse event, in 17 of 19 patients, followed by vomiting, nausea, lymphocytopenia and leukopenia.; Biopsies showed increasing CD4-positive and CD8-positive tumour-infiltrating lymphocytes with persistently low numbers of Foxp3-positive cells.
- What it means: This is the evidence behind a national approval, and it is 19 patients in a single arm. The survival figure is genuinely higher than historical expectation in recurrent glioblastoma, and the biopsy findings support the immune mechanism. It is not a randomised comparison, and the imaging pattern means the usual response criteria cannot be used, which makes an uncontrolled result harder rather than easier to interpret.
- Caveats: Single-arm, 19 patients; the comparison is with historical expectation, not a control group.; The characteristic enlargement with contrast clearing means standard response criteria do not describe what the treatment does, so almost every patient is recorded as stable disease.; Approval in Japan was conditional and time-limited under the country's scheme for regenerative and gene therapies, so confirmation is still required.

## Sources

- Nat Med 2022: https://doi.org/10.1038/s41591-022-01897-x
- PubMed: https://pubmed.ncbi.nlm.nih.gov/35864254/

## Connected records

- cancers: [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/)
- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- technologies: [Oncolytic viruses](https://onco.cc/technologies/oncolytic-virus/)
- people: [Tomoki Todo](https://onco.cc/people/tomoki-todo/)
- journals: [Nature Medicine](https://onco.cc/journals/nature-medicine/)

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