Moderna and Merck's personalized mRNA cancer vaccine cut melanoma recurrence risk by 42%

Merck $MRK and Moderna $MRNA reported detailed Phase 3 results showing that their individualized mRNA therapy, intismeran autogene, lowered the chance of relapse or death by 42% when added to Merck's Keytruda. The comparison was with Keytruda alone in patients with completely resected stage IIB-IV melanoma.

The companies said the combination cut the risk of distant metastasis or death by 38% after a median follow-up of 24.6 months. The two-year recurrence-free survival rate was 82.2% for intismeran plus Keytruda, compared with 70.0% for Keytruda alone.

Overall survival data are not mature, but the companies said they have seen a favorable trend. The study is continuing to evaluate overall survival and other endpoints.

In the first six months, efficacy of intismeran plus Keytruda was comparable with Keytruda alone, the companies said. Once patients had finished the six-month course of intismeran, a pre-specified sensitivity analysis found they were 58% less likely to experience recurrence or death.

The trial enrolled 1,137 patients, randomized 2:1 to intismeran plus Keytruda or placebo plus Keytruda. Treatment-related adverse events occurred in 95.8% of patients on the combination (723 of 755) and 90.0% of those on Keytruda alone (342 of 380). Grade 3-5 events occurred in 14.2% and 13.4% of patients, respectively. The most common events with the combination were fever, injection site pain and fatigue. The companies said no new safety signals were observed.

Moderna stock slid by up to 25% during Thursday's session, and Merck stock lost roughly 1%. Partial data leaked before the full release, according to CNBC.

The companies said they are engaging with regulatory authorities. Moderna CEO Stéphane Bancel said his firm is wrapping up an application to pursue full approval next year, according to CNBC.

“While these results are in patients with completely resected stage IIB-IV melanoma, they provide valuable insights and will help inform our understanding of intismeran as clinical research continues into other tumor types and across settings,” Georgina Long, the study’s principal investigator, said in a statement.

The companies said the results were slated for presentation at the European Society for Medical Oncology Congress 2026 and have been accepted for publication in The New England Journal of Medicine.

The companies are running nine Phase 2 and Phase 3 trials of intismeran across tumor types, including three Phase 3 trials in non-small cell lung cancer.