Three-Year Update of a Randomized Phase IIb Study of the Individualized Neoantigen Therapy Intismeran Autogene (mRNA-4157, V940) Plus Pembrolizumab Versus Pembrolizumab in Resected Melanoma

PURPOSE Primary analysis of KEYNOTE-942 (ClinicalTrials.gov identifier: NCT03897881 ) demonstrated prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) for the individualized neoantigen therapy intismeran autogene (intismeran; formerly mRNA-4157 or V940) with pembrolizumab versus pembrolizumab alone in high-risk resected melanoma. This update provides an additional year of follow-up to assess longer-term efficacy/safety. METHODS KEYNOTE-942 is a phase IIb study in patients with completely resected high-risk (stage IIIB to IV) cutaneous melanoma who were randomly assigned to receive either intismeran plus pembrolizumab or pembrolizumab alone. The primary end point was RFS; secondary end points included DMFS and safety/tolerability. Overall survival and biomarker data were exploratory. RESULTS With a median follow-up of approximately 3 years, and a minimum of approximately 2 years (median [range] 34.9 [25.1-51.0] months), the combination continued to demonstrate improvement in RFS (hazard ratio [HR], 0.510 [80% CI, 0.351 to 0.743]) and DMFS (HR, 0.384 [80% CI, 0.227 to 0.650]) compared with pembrolizumab. The safety profile was consistent with earlier findings. Most adverse events (AEs) were low-grade, with serious AEs, immune-related AEs, and grade 3/4 events comparable between the arms and no grade 4/5 events related to intismeran. CONCLUSION Intismeran plus pembrolizumab significantly prolongs RFS and DMFS compared with pembrolizumab alone for the adjuvant treatment of resected high-risk melanoma.