A personalised mRNA vaccine cut the risk of melanoma returning or the recipient dying by 42% when given alongside an immunotherapy drug, according to long-awaited trial results for what could become the first approved mRNA vaccine for cancer.

Oncologists treat a risk reduction of 10% as substantial, says Kristen Radford, an immunotherapist at Mater Research in Brisbane. A reduction of more than 40% “would send many researchers over the Moon”, adds Seth Cheetham, a geneticist at the University of Queensland in Brisbane.

The vaccine, called intismeran, is not designed to stop skin cancer developing in the first place. It is meant to prevent melanoma returning in people who have already had surgery to remove tumours.

The trial enrolled 1,137 people with moderate to advanced melanoma across 157 centres. Participants were randomly assigned to receive either the tailor-made vaccine alongside pembrolizumab, an immunotherapy drug already used to treat melanoma, or pembrolizumab plus a placebo. Georgina Long, an oncologist at Melanoma Institute Australia in Sydney who led the trial, says participants have been followed for around 25 months so far and will be monitored for several years to see whether the vaccine improves overall survival. The therapy caused no major harmful side effects, she says.

Anticipation had been building since August, when the vaccine’s developers, Merck and Moderna, announced early positive results. The full phase III data was due to be presented at the European Society for Medical Oncology meeting in Madrid on 24th October, but when results leaked online on 22nd October the companies released the key figures.

Moderna’s share price, which had been rising since August, fell by around 25% after the leak. Health-care financial analyst Evan Seigerman at BMO Capital Markets in New York told Forbes that such a reaction probably reflected “inflated expectation into the full data release, rather than a true indictment on the efficacy of the combo therapy”.

Around 15 years ago, people with advanced melanoma typically survived only months. Today nearly 55% are effectively cured with targeted drugs or immunotherapies, Long says. The combination of intismeran and pembrolizumab is aimed at people whose cancer could return after surgery and who do not respond to immunotherapy alone.

Jessamy Tiffen, a cancer geneticist at the Centenary Institute in Sydney, says the results are exciting but that only time will show how effective the treatment is beyond two years. “Cancer cells also have an insidious ability to adapt and evade whatever treatment we throw at them,” she says, noting that some people did not respond to the vaccine.

To build intismeran, the team sequenced DNA from a sample of each participant’s tumour to identify mutations in the cancer cells, which can produce proteins called neoantigens that help distinguish cancer cells from healthy ones. Long says her team will now run a statistical analysis to identify who is most likely to benefit.