In a small clinical trial, customized mRNA vaccines aimed at high-risk skin cancers demonstrated a remarkable ability to lower the risk of cancer recurrence and mortality by nearly 50% over a span of five years when compared to standard treatment alone. This finding comes from Moderna and Merck, the pharmaceutical companies collaborating on the experimental cancer vaccine known as intismeran autogene (mRNA-4157 or V940).
Thus far, these promising results have been shared through a press release earlier this week. Importantly, they align well with previously detailed analyses from the trial, which assessed recurrence and mortality rates at two and three years post-treatment. The companies have announced that additional data from this Phase 2 trial will be presented at an upcoming medical conference, and a Phase 3 trial has already commenced with complete enrollment.
The ongoing Phase 2 trial comprised 157 patients diagnosed with stage 3 or 4 melanoma, all at high risk of recurrence following surgical removal. Preventive post-surgery immunotherapy, such as Merck’s Keytruda (pembrolizumab), forms the standard treatment regimen. Keytruda functions by enabling immune cells, particularly T cells, to target and destroy cancer cells—an activity typically hindered when cancer cells bind to PD-1 receptors on T cells, thereby deactivating them. Keytruda blocks these PD-1 receptors, thus maintaining T cell activation against cancer.
During the trial, all participants received the conventional Keytruda treatment. However, they were randomized in a 2:1 ratio, with some patients receiving additional customized mRNA vaccines. These vaccines were specifically tailored to each patient's melanoma, incorporating genetic instructions to create up to 34 unique markers indicative of their mutated cancer cells. Once administered, these vaccines empower healthy cells to produce the markers, which essentially train T cells to recognize and attack the cancer cells more effectively.