A personalized mRNA cancer vaccine paired with immunotherapy has cut the risk of melanoma recurrence or death by 49% at the five-year mark — the strongest evidence yet that the mRNA technology behind the COVID vaccines can be turned against cancer.
The results, from the phase 2b KEYNOTE-942 trial, were presented June 1 at the American Society of Clinical Oncology's annual meeting in Chicago and published the same day in the Journal of Clinical Oncology. Researchers at NYU's Perlmutter Cancer Center led the study, which tested an mRNA vaccine called intismeran in combination with the immunotherapy drug pembrolizumab — better known by its brand name Keytruda.
Five years out, 68.8% of patients who received the combination were still cancer-free, compared with 49.1% of patients who received Keytruda alone. Overall survival — meaning patients alive from any cause — was 92.2% in the combination group and 71.3% in the immunotherapy-alone group. The combination also reduced the risk of cancer spreading to distant parts of the body by 59%.
'Our study offers strong evidence to melanoma patients that intismeran vaccine therapy, when used in combination with immunotherapy, can demonstrably reduce their risk of having their cancer return and improve clinical outcomes,' said senior investigator Dr. Janice Mehnert, a professor at NYU Grossman School of Medicine and director of Perlmutter's melanoma medical oncology program.
The vaccine is unusual. It is not one drug; it is a different drug for every patient. After surgery to remove a melanoma tumor, researchers analyze that specific tumor for up to 34 abnormal proteins — called neoantigens — that are unique to that individual's cancer. Those instructions are then encoded into mRNA and injected. The patient's immune system reads the message, learns to recognize those exact neoantigens, and dispatches T cells trained to hunt down any remaining cancer cells trying to grow back.
Pembrolizumab works alongside it by blocking PD-1, a 'checkpoint' that cancer cells exploit to hide from the immune system. Together, the two drugs amount to a two-part strategy: the vaccine teaches the immune system what to look for, and the immunotherapy makes sure the immune system can actually see it.
The trial enrolled 157 patients in Australia and the United States between 2019 and 2021. All had had their melanomas surgically removed before being randomized to either combination therapy or pembrolizumab alone. Side effects were considered manageable — fatigue, injection-site pain, and chills, the kind of profile familiar to anyone who has had an mRNA vaccine.
What makes the five-year data so striking is its durability. Short-term trial results in oncology often look promising and then fade as the cancer finds workarounds. Here, the benefit has held steady — the gap between the two groups has not closed.
'Our findings also serve as encouragement to cancer researchers globally that mRNA vaccines like intismeran could work well in combination with immunotherapy for other cancers whose high rates of mutations have proven difficult to target,' Mehnert said.
A phase 3 trial, the next regulatory step before potential approval, is already underway. Researchers are also testing intismeran against lung cancer and other tumor types. Funding for the study came from Moderna, which makes the vaccine, and Merck, which makes Keytruda.
Melanoma is the most aggressive form of skin cancer, with an estimated 112,000 new cases in the United States in 2026. Death rates have already been falling for a decade thanks to immunotherapy. If the phase 3 trial confirms what KEYNOTE-942 just showed, the next decade could bring a steeper drop — and a working blueprint for turning mRNA technology loose on cancers far beyond the skin.
