mRNA-4157/V940, a personalized mRNA-based cancer vaccine, in combination with the immune checkpoint inhibitor pembrolizumab improved recurrence-free survival compared with pembrolizumab alone in patients with high-risk melanoma, and clinical benefit was observed regardless of tumor mutational burden (TMB) status, according to results from the phase IIb KEYNOTE-942 clinical trial presented by Khattak et al at the American Association for Cancer Research (AACR) Annual Meeting 2023.
According to the results of the primary trial analysis, after 18 months, the recurrence-free survival was 78.6% in the combination arm and 62.2% in the pembrolizumab-alone arm, corresponding to a 44% reduction in the risk of recurrence or death in patients who received both mRNA-4157/V940 and pembrolizumab compared to those who only received pembrolizumab. The majority of treatment-related adverse events were mild, and the rates of serious adverse events were comparable between the two arms. The vaccine/pembrolizumab combination led to a similar reduction in the risk of recurrence or death in patients with high and low TMB (35% and 41%, respectively); high TMB was defined as 10 mutations per megabase.