Multinational phase 2 study of lenvatinib plus pembrolizumab for melanoma with progression on PD-(L)1 inhibitor

Effective treatments are needed for melanoma that progresses on inhibitors of PD-1 or its ligand PD-L1. The multinational phase 2 LEAP-004 study evaluated the combination of lenvatinib and pembrolizumab for unresectable stage III or IV melanoma with confirmed progressive disease within 12 weeks of the last dose of a PD-(L)1 inhibitor given alone or with other therapies. The combination resulted in objective response in 21.4% of patients (2.9% complete response) with a median duration of response of 8.3 months (range 3,2-15.9+). The median PFS and OS were 4.2 months (95% CI 3.8-7.1) and 14.0 months (10.8-NR), respectively. Grade 3-5 TRAEs occurred in 45.6% of patients; one patient died from a TRAE (decreased platelet count). The authors conclude that the combination of lenvatinib plus pembrolizumab provides clinically meaningful, durable responses of advanced melanoma with progression on prior PD-(L)1 inhibitor therapy, with a safety profile as expected.