Personalized mRNA Vaccine Cuts Melanoma Recurrence Risk by 42% in Phase 3 Trial

A personalized mRNA cancer vaccine combined with Keytruda reduced the risk of melanoma recurrence or death by 42 percent compared with Keytruda alone, according to new two-year results.

How the personalized mRNA vaccine works

The customized vaccine, called Intismeran (also known as mRNA-4157), uses synthetic messenger RNA to carry the unique genetic code for up to 34 mutations found in a patient’s cancer cells.

To create each personalized vaccine, researchers compare the genetic sequence of a patient’s cancer cells with that of healthy cells. This helps identify cancer-specific mutations that may enable the immune system to selectively target cancer cells.

Two-year melanoma trial results

Researchers evaluated recurrence-free survival (RFS), the length of time a patient remains free of returning cancer, and distant metastasis-free survival (DMFS), the length of time a patient remains free of cancer returning or spreading to another part of the body.

After two years, participants who received Intismeran plus Keytruda had a 42 percent lower risk of recurrence or death than those who received Keytruda plus a placebo, according to a hastily published press release.

Overall, 82 percent of patients in the Intismeran and Keytruda group were alive without a relapse after two years, compared with 70 percent of patients in the Keytruda and placebo group.

Fewer distant metastases with Intismeran and Keytruda

The combination also reduced the risk of distant metastases or death by 38 percent compared with Keytruda plus a placebo.

At the end of the study, 88.5 percent of patients who received Intismeran and Keytruda were alive and free of distant metastases. That compared with 80 percent of patients in the Keytruda and placebo group.

Results are weaker than the earlier Phase 2 trial

The treatment effect was not as strong as the results from a five-year Phase 2 trial. That study reported a 49 percent reduction in the risk of recurrence or death and a 59 percent reduction in the risk of distant metastases or death.

A potential advance in melanoma treatment

Even so, the findings represent an important development for patients with melanoma. Dean Lee, president of Merck Research Laboratories, described the study as the first Phase 3 trial to show clinically meaningful improvements in recurrence-free and distant metastasis-free survival compared with standard-of-care Keytruda in patients with resected melanoma.

Lee said the results set a new benchmark in adjuvant therapy and represent one of the most important advances in melanoma treatment since the advent of immunotherapy.