Randomized phase 2b trial of addition of individualized neoantigen therapy to pembrolizumab after resection of melanoma

Checkpoint inhibitors are standard adjuvant treatment for stage IIB-IV resected melanoma, but recurrence is seen in many patients. The randomized phase 2b KEYNOTE-942 in the USA and Australia evaluated addition of mRNA-4157, a novel mRNA-based individualized neoantigen therapy, to adjuvant pembrolizumab after resection of stage IIIB-IV. Patients were randomized 2:1 to mRNA-4157 plus pembrolizumab or pembrolizumab alone. The recurrence-free survival (primary endpoint) was longer in the combination therapy group than in the monotherapy group (HR 0.561; p=0.053). Grade ≥3 treatment-related adverse events occurred in 25% of patients in the combination therapy group and 18% of patients in the monotherapy group. The authors conclude that among patients with resected stage IIIB-IV melanoma, addition of mRNA-4157 to adjuvant pembrolizumab was associated with prolonged recurrence-free survival.