Merck, Moderna say personalized mRNA vaccine meets Phase 3 melanoma goals

A tumor is removed, its mutations are mapped, and the treatment is built around what remains distinctive about that cancer. That is the logic behind intismeran autogene, Moderna and Merck’s personalized mRNA therapy, which the companies say met the main goals of a Phase 3 trial in high-risk melanoma after surgery.

The study enrolled 1,137 people with cutaneous melanoma at stages IIB, IIC, III or IV. Participants were randomly assigned in a 2:1 ratio to receive either intismeran with Merck’s Keytruda or Keytruda alone. The companies reported statistically significant and clinically meaningful improvements in the trial’s two main measures, including keeping the cancer from returning or spreading, but they have not yet released the detailed figures.

The mechanism is more specific than that of a conventional vaccine. Researchers identify neoantigens—abnormal proteins associated with a patient’s tumor—and use synthetic messenger RNA to encode up to 34 of them. Healthy cells translate those instructions into protein fragments, which are presented to immune cells as targets; Keytruda helps activate T cells against tumor cells.

The result matters because this is the first positive randomized Phase 3 trial of an individualized neoantigen therapy and an mRNA-based cancer treatment, according to the companies and University of Oxford cancer expert Lennard Lee. Earlier Phase 2b results reported after five years cut the risk of recurrence or death by 49 percent and the risk of distant spread or death by 59 percent compared with Keytruda alone.

So what changes for patients? If the full data confirm the announcement, people whose melanoma has been removed could have a personalized treatment intended to find cancer cells left behind, rather than relying on one standard vaccine for everyone. But the vaccine remains investigational: detailed subgroup results, quality-of-life measurements and mature overall-survival data are not yet available, and outside scientists have not reviewed the findings. Merck and Moderna plan to present the full results and discuss possible approval with regulators; the approach is also being tested in nine Phase 2 and Phase 3 trials for lung, bladder and kidney cancers.