A personalized mRNA vaccine cut the risk of melanoma returning, or the patient dying, by 42% in a phase 3 trial, researchers reported at the European Society for Medical Oncology congress in Madrid.
The trial, INTerpath-001, tested intismeran autogene — also called mRNA-4157 or V940 — given with pembrolizumab, Merck's immunotherapy sold as Keytruda, in patients whose stage IIB to IV melanoma had been completely removed by surgery.
What the trial found
After a median follow-up of 24.6 months, the combination improved recurrence-free survival, the trial's main endpoint, with a hazard ratio of 0.58. That is a 42% lower risk of recurrence or death than pembrolizumab alone.
The data reached the public two days early. They were posted online and then removed on 22 October, and the companies released the headline numbers the same day, ahead of the presidential symposium where Georgina Long of the Melanoma Institute Australia presented the full results.
How the vaccine works
Each dose is made for one patient. Researchers sequence the mutations in that patient's tumour, select the ones most likely to be recognised by the immune system, and encode them in mRNA. Cells that take up the message display the fragments on their surface, which teaches T cells what to look for.
Because the vaccine is bespoke, manufacturing starts only after surgery and tumour sequencing. That is also why the treatment is expected to be expensive.
What it means for patients
If regulators approve it, this would be the first mRNA cancer vaccine on the market — the result of a 20-year effort that began with vaccines designed to prevent cancer rather than treat it.
Long called the findings "a foundational shift" in how the immune system is used to reduce recurrence. Robert Vonderheide, president-elect of the American Association for Cancer Research, who was not involved in the trial, told the New York Times the results rank with the field's biggest.
Merck and Moderna have not said when they will file for approval. The trial continues to follow patients for overall survival, which matters because recurrence-free survival is a proxy; a survival benefit has not yet been reported.