Severe sunburns increase the risk of developing melanoma, the most serious type of skin cancer.Credit: Olga Pankova/Getty
A personalized mRNA vaccine reduced the recipient’s risk of skin cancer recurrence or death by 42% when used in combination with an immunotherapy drug, according to highly anticipated results from what could become the first approved mRNA vaccine against cancer.
Oncologists consider a 10% risk reduction to be substantial, says Kristen Radford, an immunotherapist at Mater Research in Brisbane. A risk reduction of more than 40% “would send a lot of researchers to the Moon,” adds Seth Cheetham, a geneticist at the University of Queensland in Brisbane, Australia.
The personalized vaccine, called intismeran, is not designed to stop skin cancer, or melanoma, from growing, but to prevent it from coming back in people who have already had surgery to remove tumors.
The wait for trial results has grown since August, when the vaccine’s developers — Merck, based in Rahway, New Jersey, and Moderna, headquartered in Cambridge, Massachusetts — announced initial positive results. Data from the phase III trial will be presented at the European Society of Medical Oncology meeting in Madrid on October 24. But when the data was leaked online on October 22, the companies published the main results.
The stock price of Moderna, a pioneer in mRNA vaccine technology, had been rising since the August announcement but fell about 25% after the leak. Health-care financial analyst Evan Seigerman of BMO Capital Markets in New York told media company Forbes that such reactions in the stock market likely reflect “inflated expectations that the data will be fully released, rather than a true indictment on the effectiveness of the combination therapy.”
Chance of survival
The intismeran trial enrolled 1,137 people with moderate to advanced melanoma across 157 centers. Participants were randomly assigned to receive either a tailored vaccine (intismeran) plus pembrolizumab, an immunotherapy drug already used to treat melanoma, or pembrolizumab plus an inactive placebo. Georgina Long, trial leader and oncologist at the Melanoma Institute Australia in Sydney, says participants have so far been followed for about 25 months and will continue to be monitored for several years to determine whether the vaccine improves overall survival. She adds that the therapy did not cause any major harmful side effects.
About 15 years ago, people with advanced melanoma typically only survived a few months. Today, nearly 55 percent of people are effectively cured with targeted drugs or immunotherapies, Long says. The combination of intismeran and pembrolizumab is designed for people whose cancer might come back after surgery and who don’t respond to immunotherapy alone, she says.
Jessamy Tiffen, a cancer geneticist at the Centenary Institute in Sydney, says the trial results are exciting, but only time will tell how effective the treatment is beyond two years. “Cancer cells also have an insidious ability to adapt and evade the treatments we give them,” she says. Additionally, some people did not respond to the vaccine, she said.
Long says his team will perform a statistical analysis to identify who is most likely to benefit from the treatment.
Hard to do
To develop intismeran, Long and his colleagues sequenced DNA from a sample of each participant’s tumor to identify mutations in the cancer cells. These mutations can give rise to proteins called neoantigens, which help distinguish cancer cells from healthy cells.
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