Personalized mRNA Vaccine Cuts Melanoma Recurrence or Death Risk by 42%

A personalized mRNA vaccine combined with the immunotherapy drug pembrolizumab reduced the risk of melanoma recurrence or death by 42% in a Phase III clinical trial. The long-awaited results could make the treatment the first approved mRNA vaccine for cancer.

Kristen Radford, an immunotherapist at Mater Research in Brisbane, said oncologists consider a 10% reduction in risk to be significant. Seth Cheatham, a geneticist at the University of Queensland in Brisbane, Australia, said that a reduction of more than 40% “would make a lot of researchers over the moon.”

The personalized vaccine, called Intismeran, is not designed to prevent melanoma from developing. Instead, it aims to stop the cancer from returning in people who have already undergone surgery to remove a tumor.

Expectations for the results had been high since August, when the vaccine developers, Merck & Co. of Rahway, New Jersey, and Moderna of Cambridge, Massachusetts, announced promising early findings. Data from the Phase III trial will be presented at the European Society of Medical Oncology meeting in Madrid on October 24. However, after the results were leaked online on October 22, both companies announced significant findings.

Moderna shares, which had risen after the August announcement, fell by about 25% following the leak. Evan Sagerman, a health-care finance analyst at BMO Capital Markets in New York City, told Forbes that the market reaction might reflect “increased expectations for full data release rather than a real indictment of the effectiveness of the combination therapy.”

How the melanoma vaccine trial worked

The Intismeran trial enrolled 1,137 people with moderate to aggressive melanoma at 157 sites. Participants were randomly assigned to receive either the tailored vaccine alongside pembrolizumab or pembrolizumab combined with an inactive placebo.

Pembrolizumab is already used to treat melanoma. Georgina Long, an oncologist and study director at the Melanoma Institute Australia in Sydney, said participants had been followed for about 25 months and would continue to be monitored for several years to determine whether the vaccine improves overall survival.

Long said the treatment did not cause any significant adverse side effects. The combination is intended for people whose cancer may return after surgery and who do not respond adequately to immunotherapy alone.

Could personalized mRNA vaccination improve melanoma survival?

About 15 years ago, people with advanced melanoma typically lived for only a few months. Today, nearly 55% are effectively cured with targeted drugs or immunotherapy, Long said.

Jessamy Tiffen, a cancer geneticist at Sydney’s Centenary Institute, described the trial results as interesting but said more time would be needed to determine how effective the treatment remains beyond two years.

“Cancer cells also have the insidious ability to adapt and evade whatever treatments we give them,” Tiffen said. She added that some participants might not have mounted a response to the vaccine.

Long said her team will conduct statistical analyses to determine which patients are most likely to benefit from the treatment.

How the personalized cancer vaccine is made

To develop Intismeran, Long and her colleagues sequenced DNA from each participant’s tumor sample to identify mutations in the cancer cells. These mutations can produce proteins called neoantigens, which help distinguish cancer cells from healthy cells.