After the operation, a new weapon against recurrence
Removing a melanoma does not always mean that the risk is gone. Even after complete surgery, invisible cancer cells can persist in the body and sometimes cause recurrence or metastasis. For patients, the wait and monitoring following the operation can therefore remain a source of worry.
This is where intismeran autogene, also called V940 or mRNA-4157, comes into play. This personalized therapeutic vaccine is designed to help the immune system recognize cancer cells that may remain after surgery.
In the international phase 3 INTerpath-001 trial, 1,137 patients with high-risk cutaneous melanoma, completely removed by surgery, received either the vaccine combined with Keytruda immunotherapy or a placebo combined with Keytruda immunotherapy.
After a median follow-up of 24.6 months, the results are encouraging: the combination reduced the risk of recurrence or death by 42% and that of distant metastases or death by 38%, compared to Keytruda alone.
In practice, after two years, 82.2% of patients who received the combination had not experienced a recurrence, compared to 70% in the control group.
These results, announced by Merck and Moderna and presented at the 2026 Congress of the European Society for Medical Oncology (ESMO), in Madrid, have been accepted for publication in the New England Journal of Medicine.
They mark an important step: it is the first phase 3 trial to show a significant benefit of this personalized approach on survival without recurrence and without distant metastases in patients operated on for melanoma.
A tailor-made vaccine to teach the body to recognize cancer
How does this vaccine work? Unlike preventive vaccines, intismeran autogene is designed from mutations specific to each patient’s tumor.
Researchers analyze a tumor sample and the patient’s healthy DNA to identify up to 34 neoantigens, protein fragments characteristic of cancer. This information is used to make a synthetic messenger RNA specific to each patient, which gives the body’s cells the necessary instructions to produce these fragments and present them to the immune system.
The goal is to train T lymphocytes, immune cells capable of recognizing and eliminating cancer cells, to target the particularities of the tumor.
The idea is to give the immune system a sort of robot portrait of the cancer, to help it spot any residual cells after the operation.
In the trial, the advantage of the combination was especially evident after the first six months, once the vaccination schedule had been initiated. Additional analysis then showed a 58% reduction in the risk of recurrence or death. This result reinforces the interest of this approach, without replacing the main result of the trial.
Encouraging results, but limits not to be forgotten
Enthusiasm must nevertheless remain measured. If the vaccine improves the chances of remaining recurrence-free, its effect on overall survival is not yet established. Researchers are continuing to monitor patients to determine if the combination actually allows them to live longer.
Tolerance is also an essential element. The most common adverse reactions with the combination were fever (52.2%), pain at the injection site (51%) and fatigue (38.5%).
Treatment-related adverse events were reported in 95.8% of patients receiving the vaccine and Keytruda, compared to 90% with Keytruda alone. Grade 3 to 5 events, the most severe, concerned 14.2% and 13.4% of patients, respectively. No new safety signals have been identified.
“The innovative results of the INTerpath-001 study could profoundly transform the adjuvant management of patients with early-stage melanoma.”said Professor Georgina Long, principal investigator of the study, medical director of the Melanoma Institute Australia and chair of medical oncology and translational melanoma research at the University of Sydney.
Towards a new generation of cancer treatments?
Intismeran autogene is also being studied in other cancers, including lung, kidney and bladder. But the results obtained in melanoma do not allow us to assume its effectiveness against these other tumors.
Merck and Moderna have initiated procedures with regulatory authorities with a view to possible authorization. However, the vaccine remains experimental and is not yet a routinely available treatment.
For patients, this advance carries an important promise: going beyond the treatment of the visible tumor to better prevent its return. It also opens up a perspective for personalized medicine, which seeks to adapt treatments to the biological characteristics of each cancer.
It will still be necessary to confirm the sustainability of the benefit and its effect on survival. But a step has just been taken: a personalized anticancer vaccine demonstrates, in phase 3, that it can improve results after melanoma surgery. This is a major breakthrough, without yet being a guarantee of a cure.