Moderna and Merck report longer recurrence-free survival with mRNA cancer vaccine plus Keytruda in melanoma

Moderna and Merck announced positive results from a late-stage clinical trial testing a personalized mRNA cancer vaccine, intismeran, combined with the immunotherapy pembrolizumab (Keytruda) in patients with high-risk melanoma. The study enrolled 1,137 people with stage 2 to stage 4 disease who had undergone surgery to remove their tumors.

Participants were randomly assigned to receive either the combination of intismeran and Keytruda or Keytruda alone for just over a year. Patients receiving the combination lived longer without any recurrence of their cancer and had fewer instances of distant spread compared with those receiving Keytruda alone, the current standard of care.

Intismeran is an autologous therapy: each patient’s tumor is sequenced to identify its unique mutations, custom mRNA encoding those mutations is manufactured, and the resulting vaccine is administered to teach the immune system to recognize residual cancer cells. The mRNA platform allows this personalized manufacturing to be completed in a matter of weeks.

Keytruda works by blocking the PD-1 pathway, preventing cancer cells from hiding from the immune system. The companies said the combination demonstrated a statistically significant improvement in recurrence-free survival, the trial’s primary endpoint, though specific hazard ratios and median survival times were not disclosed in the announcement.

Earlier data presented at the ASCO meeting this year from a Phase 2 study showed the combination reduced the risk of recurrence by 49% and the risk of distant metastasis or death by 59% compared with Keytruda alone. The Phase 3 results appear consistent with those findings.

Because Keytruda is already an approved standard treatment, regulators allowed the trial to combine the experimental vaccine with it rather than using a placebo control, ensuring all participants received at least the current standard of care. Moderna CEO Stéphane Bancel said the company is now studying intismeran in earlier-stage lung cancer and in kidney, pancreatic, and bladder cancers across nine ongoing trials.

The mRNA vaccine approach aims to offer a personalized treatment with a manageable safety profile, potentially allowing administration in outpatient or community settings. Researchers caution that longer follow-up is needed to confirm overall survival benefit and to define the therapy’s role across different tumor types.