Moderna's personalised mRNA vaccine and melanoma recurrence: what the phase 2b trial actually showed, and what comes next

The personalised mRNA-4157 (V940) vaccine combined with pembrolizumab after complete resection of melanoma prolonged recurrence-free survival compared with pembrolizumab alone in the randomised phase 2b KEYNOTE-942 trial (Lancet 2024, n=157: 107 vs 50 patients). At 18 months, 79% of patients in the combination arm versus 62% on pembrolizumab remained recurrence-free (HR 0.561; 95% CI 0.309-1.017; p=0.053), with recurrence in 22% versus 40%. Despite headlines about stopping recurrence, the result did not meet the conventional threshold for statistical significance — the confidence interval crosses 1.0 — and comes from a phase 2b trial rather than a registrational phase 3. Grade 3 or higher adverse events occurred in 25% versus 18% of patients.