# IGNYTE: an engineered herpes virus with nivolumab in melanoma that had already failed anti-PD-1 therapy

Source: https://onco.cc/key-papers/paper-wong-ignyte-rp1-nivolumab-jco-2025/  
OnCo record `paper-wong-ignyte-rp1-nivolumab-jco-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In melanoma that had already stopped responding to immunotherapy, injecting an engineered herpes virus alongside nivolumab shrank tumours in about a third of patients, including tumours that were never injected.

## Summary

Registrational cohort of 140 patients with advanced melanoma and confirmed progression on anti-PD-1 therapy given as the last prior treatment for at least eight weeks. Vusolimogene oderparepvec, a herpes simplex virus type 1-based oncolytic immunotherapy, was given into tumours for up to eight doses of up to 10 mL, with nivolumab for up to two years. The objective response rate was assessed by independent central review.

Confirmed objective response rate was 32.9 per cent (95% CI 25.2 to 41.3), with complete response in 15.0 per cent. Responses occurred with similar frequency, depth, duration and timing in injected and uninjected lesions, including visceral ones, which is the evidence for a systemic effect rather than a local one. Median duration of response was 33.7 months. Overall survival was 75.3 per cent at one year and 63.3 per cent at two. Treatment-related adverse events were grade 1 or 2 in 77.1 per cent, grade 3 in 9.3 per cent and grade 4 in 3.6 per cent, with no grade 5 events. 65.7 per cent had primary resistance to anti-PD-1 therapy and 46.4 per cent had received both anti-PD-1 and anti-CTLA-4 therapy.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Journal of Clinical Oncology
- Year: 2025
- DOI: 10.1200/JCO-25-01346
- Authors: Wong MK, Milhem MM, Sacco JJ, et al.
- Findings: Confirmed objective response rate 32.9 per cent (95% CI 25.2 to 41.3) by independent central review, with 15.0 per cent complete responses.; Responses occurred with similar frequency, depth, duration and kinetics in uninjected lesions, including visceral lesions, as in injected ones.; Median duration of response 33.7 months (95% CI 14.1 to not reached).; Overall survival 75.3 per cent at one year and 63.3 per cent at two years.; Treatment-related adverse events: 77.1 per cent grade 1 or 2, 9.3 per cent grade 3, 3.6 per cent grade 4, no grade 5.
- What it means: The uninjected-lesion responses are the most important result any oncolytic virus trial has produced, because they are the first strong clinical evidence that the mechanism is systemic immunity rather than local lysis. The caution is the same as always: this is a single-arm cohort in a population with no standard option, and the randomised confirmatory trial has not read out.
- Caveats: Single-arm, so the contribution of nivolumab alone in anti-PD-1-failed melanoma cannot be separated out; some patients respond to re-challenge.; Accelerated approval rests on response rate; the randomised IGNYTE-3 trial has to confirm it.; Still requires injectable lesions, so the population is selected for accessible disease.

## Sources

- JCO 2025: https://doi.org/10.1200/JCO-25-01346
- PubMed: https://pubmed.ncbi.nlm.nih.gov/40627813/

## Connected records

- cancers: [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [Melanoma](https://onco.cc/cancers/melanoma/)
- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- technologies: [Oncolytic viruses](https://onco.cc/technologies/oncolytic-virus/)
- drugs: [Nivolumab](https://onco.cc/drugs/nivolumab/), [Vusolimogene oderparepvec](https://onco.cc/drugs/vusolimogene-oderparepvec/)
- companies: [Replimune](https://onco.cc/companies/replimune/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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