Personalized mRNA cancer vaccine cuts melanoma recurrence risk by 42% in Phase 3 trial

For decades, a vaccine that could stop cancer from coming back after surgery was medicine's most wanted idea and its most stubborn failure. On Saturday in Madrid, researchers presented the first Phase 3 trial to make it real: a personalized mRNA vaccine, built from the genetic fingerprint of each patient's own tumor, reduced the risk of melanoma returning or killing the patient by 42% compared with the best standard treatment alone.

The results — from a trial of more than 1,100 patients at 157 sites worldwide — were presented at the European Society for Medical Oncology Congress 2026 by Georgina Long, a medical oncologist at Melanoma Institute Australia and the trial's global principal investigator. They are set to be published in the New England Journal of Medicine. Moderna and Merck, the vaccine's developers, released the data early on Thursday after reports that it had been published online and then taken down.

These findings are a foundational shift in our approach to cancer: harnessing the immune system in a more personalized way to reduce the risk of melanoma recurrence or death. This has not been achieved before in the history of cancer drug development.— Georgina Long, Medical Oncologist, Melanoma Institute Australia

The vaccine, called intismeran autogene until it receives a brand name, works in combination with Keytruda (pembrolizumab), an immunotherapy drug already approved and widely used for melanoma. The combination also cut the risk of distant metastasis or death compared with Keytruda plus a placebo, according to the multi-source summary of the data.

For patients who were still cancer-free six months after starting treatment, the risk reduction for recurrence or death was even sharper — 58% compared with Keytruda alone, according to Science Alert.

The vaccine uses the same mRNA platform that underpins Moderna's Covid-19 vaccine, but its purpose is entirely different. Once a melanoma tumor is surgically removed, a sample is sequenced. Scientists identify up to 34 tumor-specific neoantigens — molecular markers unique to that patient's cancer — and design a vaccine that essentially creates a personalized 'wanted poster' for the immune system. The mRNA instructs the body's own cells to display that poster, so immune cells learn exactly what to find and destroy.

Cancer can fool the immune system with a fake friendly handshake, so the immune system thinks the cancer cell is normal. Pembrolizumab blocks the handshake, allowing immune cells to recognize the cancer and attack it, but it is the same drug for everyone.— Georgina Long, Medical Oncologist, Melanoma Institute Australia

Keytruda, approved in 2014, works by lifting a kind of molecular disguise that cancer cells use to hide from the immune system. It was famously used to treat President Jimmy Carter for melanoma that had spread to his liver and brain; Carter announced he was cancer-free in December 2015, according to CNN. The new vaccine is designed to make Keytruda's immune-system activation more precise — targeted at the specific cancer cells that were in that patient's body, rather than broadly unleashing immune activity.

This personalized cancer vaccine is a specific type of treatment that boosts the body's immune response only against the cancer cells that are there, and therefore it is a much more targeted immune boost directly against that patient's individual tumor.— Dr. Michael Postow, Chief of the Melanoma Service, Memorial Sloan Kettering Cancer Center

The trial enrolled patients with high-risk melanoma — those whose cancer had already spread to lymph nodes or grown to a significant thickness in the skin, making recurrence after surgery a serious probability. One participant, 59-year-old Beth Ryzyk, was diagnosed with stage IIIC melanoma in December 2023. She still does not know whether she received the vaccine or the placebo — the trial remains blinded — but more than a year after finishing treatment, she is cancer-free.

I'm good; sometimes I even forget about it. It's always in the back of your mind … but they're watching.— Beth Ryzyk, Trial Participant

The experimental vaccine was given as an intramuscular injection every three weeks for up to nine doses, while Keytruda was administered by intravenous infusion every six weeks for up to about a year, according to CNN. Ryzyk said that after each treatment she felt 'a little sick, just a little flu and kind of down the next day' — a side-effect profile consistent with immune activation.

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 among 'our biggest breakthroughs,' according to Science Alert.

The critical caveat is overall survival — whether the treatment actually helps patients live longer. The companies said it is too early to report that data, but that 'a favorable trend' in improving overall survival 'has been observed,' according to CNN. The trial will continue until that measure can be properly assessed.

Merck and Moderna said they are 'engaging with regulatory authorities,' language that implies an FDA approval filing could come soon. Analysts at RBC Capital Markets said the FDA is likely to approve the therapy next year, according to CNN. In Australia — which has one of the highest melanoma rates in the world, where one person dies from the disease every six hours according to Science Alert — the regulatory review process could take several years.

The companies are already testing the mRNA vaccine technology in lung, pancreatic, kidney, and bladder cancers, according to the multi-source data summary. But the path is not guaranteed: recent randomized trials testing mRNA vaccines for colorectal cancer and head and neck cancer failed to reduce recurrence, according to Science Alert, making the melanoma result both more significant and a reminder that success in one tumor type does not automatically transfer to others.

The hope for the near future is that it may not only improve outcomes for melanoma patients with advanced disease, but also those with other types of cancer where current immunotherapies are poorly effective.— Alex Menzies, Medical Oncologist, Melanoma Institute Australia

Wall Street's reaction on Thursday was mixed. Moderna's stock fell 18% on the day the data were released, with analysts noting the results were somewhat less dramatic than those seen in an earlier, smaller Phase 2 trial. Merck's shares declined 1.8%. Even so, Moderna's stock remained more than 500% higher year-to-date as of Thursday, according to CNN, reflecting investor conviction — and anxiety — about whether mRNA technology can become the company's next major platform after Covid vaccines.

This new vaccine is something that we've never really seen before in terms of the efficacy that it has demonstrated and the way that it works.— Dr. Michael Postow, Chief of the Melanoma Service, Memorial Sloan Kettering Cancer Center

Why it matters — If regulators approve the vaccine and the approach scales to other cancers, it would mark the first time mRNA technology has been used to treat an existing disease — not just prevent infection — potentially opening a new chapter in how cancer is managed after surgery.

Reported by nytimes.com, statnews.com, cnn.com, sciencealert.com