mRNA cancer vaccine shows protection at 5-year follow-up, Moderna and Merck say

In a recent clinical trial, personalized mRNA vaccines targeting high-risk skin cancers have shown a remarkable ability to lower the chances of cancer recurrence and mortality by nearly 50% over a five-year period compared to standard therapies. This significant finding was reported by pharmaceutical giants Moderna and Merck, who are jointly developing the experimental cancer vaccine known as intismeran autogene (mRNA-4157 or V940). While the companies have initially shared only top-line results through a press release, these findings closely mirror earlier, detailed analyses from the same trial, which monitored recurrence and death rates at two and three years post-treatment. Further insights from this Phase 2 trial are expected to be unveiled at an upcoming medical conference, and a Phase 3 trial is already in progress with patient enrollment completed. The ongoing Phase 2 trial involved 157 participants diagnosed with stage 3 or stage 4 melanoma, all deemed at high risk for cancer recurrence following surgical intervention. The standard approach to mitigate recurrence typically includes immunotherapy, such as Merck's Keytruda (pembrolizumab). This medication enhances the immune system's ability to combat cancer by enabling T cells to attack and destroy cancer cells, which they are naturally designed to do. However, many cancer types, including melanoma, can evade T cell responses by binding to PD-1 receptors, effectively disabling these immune cells. Keytruda counters this by blocking PD-1 receptors, allowing T cells to remain active and target cancer cells. In the trial, every participant received Keytruda as part of their treatment plan, but they were randomly assigned in a 2:1 ratio to also receive the customized mRNA vaccines. These vaccines were meticulously designed for each patient’s unique melanoma profile, delivering genetic instructions that enable healthy cells to produce up to 34 distinct markers of their mutated cancer cells. This process equips T cells with the necessary information to recognize and attack the cancer effectively.