New Jersey: A personalised mRNA based cancer treatment developed by Merck and Moderna has shown positive results in a Phase 3 trial involving patients with completely resected high risk melanoma, marking an important development in personalised cancer treatment.
The treatment, known as intismeran autogene, is also known as V940 or mRNA 4157. It is being developed in combination with Merck's cancer immunotherapy Keytruda, also known as pembrolizumab.
Merck and Moderna announced the positive results on August 19 after a prespecified interim analysis of the Phase 3 INTerpath 001 trial. The study met its primary endpoint of recurrence free survival and a key secondary endpoint of distant metastasis free survival. The companies said the improvements compared with Keytruda alone were statistically significant and clinically meaningful.
The trial enrolled 1,137 patients with completely resected stage IIB, IIC, III or IV cutaneous melanoma. The patients had undergone surgery to remove their cancer and were then randomly assigned in a 2 to 1 ratio to receive either intismeran with Keytruda or Keytruda alone.
The treatment is different from a conventional vaccine. Instead of preventing an infection, it is designed to help the immune system recognise and attack cancer cells that may remain in the body after surgery.
A sample of the patient's tumour is analysed to identify mutations specific to the cancer. The information is then used to create an individualised mRNA treatment designed to train the immune system to recognise those tumour targets. Each treatment can encode up to 34 tumour specific neoantigens.
Keytruda works in a different but complementary way. It is an immune checkpoint inhibitor that helps the body's immune system attack cancer. The Phase 3 trial therefore tested whether adding the personalised mRNA treatment could improve the results achieved with Keytruda alone.
The companies said the results represent the first positive Phase 3 readout for an individualised neoantigen therapy and an mRNA based cancer treatment. The result is also the first Phase 3 study to show a clinically meaningful improvement over Keytruda alone in this setting, according to the companies.
However, the full numerical results from the Phase 3 trial have not yet been released. The companies have not disclosed the exact reduction in the risk of recurrence or distant spread. Overall survival data are also not yet mature, so it is too early to say whether the treatment helps patients live longer.
The companies said the safety findings were consistent with previous experience and that no new safety signals were identified. The study will continue to evaluate overall survival and other measures, including safety, tolerability and quality of life.
The latest results build on evidence from an earlier Phase 2b study called KEYNOTE 942. Five year follow up data from that study, presented at the 2026 American Society of Clinical Oncology meeting, showed that patients receiving intismeran with Keytruda had a 49 percent lower risk of recurrence or death and a 59 percent lower risk of distant metastasis or death compared with patients receiving Keytruda alone.
Those figures come from the earlier Phase 2b study and should not be confused with the newly announced Phase 3 results. Detailed results from the Phase 3 trial are expected to be presented at an upcoming international medical meeting.
The development follows a partnership between Merck and Moderna that began in 2016. Moderna brought its mRNA technology to the partnership, while Merck contributed its experience with Keytruda and cancer immunotherapy.
Melanoma was an important setting for testing the treatment because the disease can contain many genetic mutations that may provide targets for the immune system. The companies also had previous evidence that Keytruda could be effective against melanoma.
The treatment remains investigational and has not been approved for routine use. Merck and Moderna plan to present the complete Phase 3 findings and engage with regulatory authorities on submissions for approval.
The companies are also studying intismeran in other cancers, including non small cell lung cancer, bladder cancer and kidney cancer. These studies are still ongoing, and there is not yet evidence that the treatment will work across different types of cancer.
The latest findings therefore represent an important step rather than the arrival of a proven cancer cure. The size of the benefit, long term survival results and regulatory decisions will help determine how widely the treatment can eventually be used.
For now, the positive Phase 3 findings provide stronger evidence that personalised mRNA technology may have a meaningful role in treating high risk melanoma when combined with established immunotherapy.