Personalized mRNA Vaccine Helps Prevent Melanoma Recurrence in Late-Stage Trial

Moderna and Merck announced this week that a late-stage clinical trial of their personalized mRNA cancer vaccine, intismeran, showed clinically meaningful results in preventing the return and spread of melanoma. The trial enrolled 1,137 patients whose advanced melanoma had been surgically removed but was considered at high risk of recurrence. All participants received pembrolizumab, an immunotherapy drug sold as Keytruda, while roughly half also received intismeran and the other half received a placebo in a double-blind design.

Intismeran is an individualized neoantigen therapy created for each patient over approximately six weeks. Researchers sequence the patient's tumor to identify unique mutations that produce neoantigens — proteins on the surface of cancer cells. The vaccine uses mRNA technology, similar to that used in COVID-19 vaccines, to train the immune system to recognize and attack cells carrying those specific neoantigens.

According to the companies, patients who received both intismeran and pembrolizumab lived longer without cancer recurrence than those who received pembrolizumab alone. They also went longer without developing new lesions outside the original cancer site. The drugmakers described the results as clinically meaningful but did not release detailed numerical data, stating they plan to present full findings at an upcoming international medical meeting and share them with regulatory authorities.

Earlier this year, Moderna and Merck reported results from a midstage trial showing the combination reduced the risk of melanoma recurrence or spread by 49 percent after five years compared to pembrolizumab alone. Melanoma is the deadliest form of skin cancer, causing an estimated 8,510 deaths annually in the United States. While early-stage melanoma is highly treatable, advanced cases that have spread deeper or to other organs remain difficult to manage.

Independent experts called the results promising and consistent with smaller recent studies. Jedd Wolchok, director of the Meyer Cancer Center at Weill Cornell Medicine, who was not involved in the trial, said the achievement establishes personalized cancer vaccines as a potential new addition to standard therapy. He noted that producing a vaccine from a patient's tumor sequencing would have been considered science fiction 15 to 20 years ago.

The trial focused exclusively on melanoma, but researchers say the same personalized mRNA approach could potentially be applied to other cancers and rare genetic conditions. Personalized mRNA vaccines are currently in development for pancreatic, stomach, kidney, bladder, colon, and lung cancers. Robert Vonderheide, director of Penn Medicine's Abramson Cancer Center and president-elect of the American Association for Cancer Research, said there is reason to hope that multiple ongoing studies will yield positive results in the coming years.

Moderna and Merck have not yet submitted a regulatory application for intismeran. The timeline for potential approval and broader clinical use will depend on the detailed data review by regulatory agencies. The companies also noted that the six-week manufacturing process for each personalized vaccine presents logistical considerations for widespread implementation.

Melanoma accounts for a small percentage of skin cancer cases but the vast majority of skin cancer deaths. The trial results represent a step toward adjuvant therapy that is tailored to the molecular profile of each patient's tumor, rather than a one-size-fits-all approach.