First successful phase 3 trial of a personalised mRNA cancer vaccine in melanoma (INTerpath-001)

The phase 3 INTerpath-001 trial met its primary endpoint of recurrence-free survival (RFS) and the key secondary endpoint of distant metastasis-free survival (DMFS) in 1,137 patients with completely resected stage IIB-IV cutaneous melanoma, randomised 2:1 to the personalised mRNA vaccine intismeran autogene (mRNA-4157) plus pembrolizumab or to pembrolizumab alone. The sponsors (Merck and Moderna) describe this as the first positive phase 3 readout for an individualised neoantigen therapy and for an mRNA-based cancer therapy; each dose is built from sequencing of the individual patient's tumour, with up to 34 neoantigens selected by algorithms that predict binding to T-cell receptors (mechanism as described by the NCI). Phase 3 effect sizes were not disclosed - the data are to be presented at a forthcoming international medical meeting and shared with regulators - and the safety profile was consistent with prior reports, with no new signals. In the earlier phase 2b KEYNOTE-942 study (n=157), the 5-year update reported a hazard ratio of 0.51 (95% CI 0.29-0.89) for RFS and 0.41 (95% CI 0.20-0.84) for DMFS.