New vaccine slashes risk of skin cancer recurring by nearly half

By Stephen Beech

A new melanoma vaccine slashes the risk of the most deadly form of skin cancer recurring by almost half, according to new research.

The combination of the vaccine and a drug, which both harness the immune system to attack cancer cells, has proven successful in cutting the risk of melanoma recurrence and death by 49%, say scientists.

The reduction was calculated five years after patients had their tumors surgically removed and remains unchanged.

The study, led by researchers from NYU Langone Health, tested the vaccine — called intismeran — in combination with mainstay immunotherapy pembrolizumab in 107 patients.

The participants had been randomly chosen after melanoma surgery to determine whether the combination therapy prevented their cancer from recurring.

Intismeran is a personalized immunotherapy strategy that is developed with information from a patient's individual tumor.

The results were compared with those from a randomly selected group of 50 melanoma patients who had only received pembrolizumab after surgery, a current standard of care.

After five years of follow-up, 68.8% of patients who took the combination therapy remained cancer free while 49.1% of the patients in the pembrolizumab-alone group had no signs of cancer.

The researchers said that means that adding intismeran to pembrolizumab reduced the risk for recurrence or death by 49%.

The combination therapy also reduced the risk of distant metastasis — the spread of cancer to another part of the body — by 59%.

Overall survival, meaning no death from cancer or any other cause, was 92.2% for the vaccine with immunotherapy group, while for the immunotherapy-alone group it was 71.3%.

Study senior investigator Janice Mehnert, of NYU Grossman School of Medicine, said: "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.

"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."

She says the results highlight the role of T cells, which are capable of attacking viruses as well as cancers.

To spare normal cells, Mehnert explained that the immune system uses checkpoint molecules on T cell surfaces to "turn off" their attack against viruses when they clear the infection.

She said the body may recognize tumors as abnormal, but cancer cells hijack checkpoints to turn off and evade immune responses.

Immunotherapies such as pembrolizumab seek to block checkpoints, specifically the PD-1 protein receptor, making cancer cells more "visible" and vulnerable again to immune cells.

Mehnert says immunotherapies, such as PD-1 inhibitors like pembrolizumab, have become the mainstay for treating melanoma, although they do not work for all patients because melanoma cells, known for their ability to evade the immune system, can become resistant to immunotherapy.

For that reason, researchers have looked at adding vaccines.

The vaccine intismeran is based on messenger RNA, a chemical cousin of DNA that provides cells with instructions for making proteins.

Intismeran and other mRNA cancer vaccines are meant to teach the immune system to recognize cancer cells as different from normal cells.

In designing a vaccine against melanoma, scientists attempted to trigger an immune response to specific abnormal proteins, called neoantigens, made by cancer cells.

Because the study volunteers all had their tumors removed, the research team was able to analyze their cells for 34 neoantigens that were specific to each melanoma and create a personalized vaccine for each patient.

As a result, T cells specific to the neoantigen proteins encoded by the mRNA were produced. Those T cells could then attack any melanoma cells trying to grow or spread.

Results of the phase 2b trial, known formally as KEYNOTE-942, are due to be presented at the annual meeting of the American Society of Clinical Oncology next month in Chicago.

The findings are due to be published at the same time in the society's Journal of Clinical Oncology.

For the KEYNOTE-942 trial, patients were enrolled at cancer centers in Australia and the United States from 2019 to 2021.

All were men and women who had had surgery to remove their melanoma tumors.

Seven patients in each treatment group died during follow-up, most from cancer.

Side effects were considered manageable and included fatigue, pain at injection sites, and chills.

Mehnert said that a phase 3, multicenter trial is already underway to determine if intismeran helps as a first-line therapy in combination with pembrolizumab for melanoma.

The vaccine is already being tested to see if it also works to prevent recurrence of lung and other cancers.