Personalized mRNA vaccine cuts melanoma recurrence and death risk by 42% in Phase 3 trial

Merck and Moderna said their personalized mRNA melanoma vaccine, intismeran (mRNA-4157), combined with Merck’s Keytruda, lowered the risk of death or cancer recurrence by 42% compared with Keytruda alone in a Phase 3 trial involving 1,137 patients with stage IIB-IV melanoma that had been surgically removed. After two years, 82% of patients receiving the vaccine-Keytruda regimen were alive without recurrence, versus 70% in the Keytruda-placebo group. The same combination also reduced the risk of distant metastasis or death by 38%, with 88.5% of those patients free of distant metastasis compared with 80% on standard therapy.

The trial randomized participants in a 2-to-1 ratio to receive either the personalized vaccine plus Keytruda or Keytruda with a placebo. The vaccine encodes up to 34 patient-specific tumor mutations, enabling the immune system to target cancer cells more precisely.

"From the beginning, we believed mRNA technology could make it possible to develop cancer treatments uniquely matched to each patient’s tumor," said Moderna CEO Stéphane Bancel in a statement.

"The trial results mark a defining moment for that vision and show what’s possible when we rethink how medicines are made," Bancel added.

Dean Li, president of Merck Research Laboratories, called the study "the first Phase 3 study to demonstrate a clinically meaningful improvement in recurrence-free and distant metastasis-free survival over standard-of-care Keytruda in patients with resected melanoma, setting a new benchmark in the adjuvant setting."

The companies are engaging regulatory authorities for approval, and the full data have been accepted for publication in the New England Journal of Medicine. Earlier Phase 2 results had shown even larger risk reductions, but the Phase 3 outcomes still represent a notable advance in adjuvant melanoma therapy.