Moderna, Merck Find 42% Lower Melanoma Recurrence-or-Death Risk

Moderna and Merck released Phase 3 results showing that their investigational personalized mRNA therapy, intismeran autogene, lowered the risk of melanoma recurrence or death when added to Keytruda after surgery.

The INTerpath-001 trial enrolled 1,137 patients with high-risk stage IIB-IV cutaneous melanoma that had been completely removed. Participants were randomly assigned in a 2:1 ratio to receive intismeran plus Keytruda or a placebo plus Keytruda. Intismeran is designed using DNA from a patient’s tumor and normal cells.

After a median 24.6 months of follow-up, the primary analysis found a hazard ratio of 0.58 for recurrence or death (95% confidence interval, 0.45-0.75; p<0.001). That result represents a 42% lower risk of recurrence or death. Estimated two-year recurrence-free survival was 82.2% with intismeran and Keytruda, compared with 70.0% with Keytruda alone.

The 42% result applies to the combined outcome of recurrence or death. It does not establish that deaths alone fell by 42%. Overall-survival data remain immature, and the study will continue to track that outcome.

The combination also lowered the risk of distant metastasis or death by 38%. Estimated two-year distant metastasis-free survival was 88.5%, compared with 80.2% in the control group.

Grade 3-5 treatment-related adverse events occurred in 14.2% of patients receiving intismeran and Keytruda and 13.4% of those receiving Keytruda alone. The most commonly reported events with the combination were fever, injection-site pain and fatigue.

The companies are engaging with regulatory authorities, and the results have been accepted for publication in The New England Journal of Medicine. The findings are scheduled for presentation Saturday, Oct. 24, at 10:30 a.m. ET (14:30 UTC) at the European Society for Medical Oncology Congress.