Lenvatinib plus pembrolizumab in advanced melanoma with disease progression

The combination of lenvatinib plus pembrolizumab has shown promising results in the LEAP-004 study in patients with advanced melanoma with disease progression after previous treatment with PD-(L)1 inhibitors.

There is an urgent need for treatment options for patients with melanoma with disease progression after treatment with PD-(L)1 inhibitors. In LEAP-004, a phase II study, 103 patients were treated with the combination of lenvatinib plus pembrolizumab. Participants were patients with unresectable stage III-IV melanoma with disease progression within 12 weeks of the last dose of a PD-(L)1 inhibitor alone or in combination with other therapies, including CTLA-4 inhibitors.

They received lenvatinib 20 mg orally once daily plus ≤ 35 doses of pembrolizumab 200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity. After a median follow-up of 15.3 months, the overall response rate (ORR) was 21.4%. In the 30 patients with progressive disease who previously received anti-PD-1 plus anti-CTLA-4, the ORR was 33.3%.

3 (2.9%) patients had a complete response and 19 (18.4%) a partial response. The median duration of response was 8.3 months. Median progression-free survival was 4.2 months (95% CI 3.8-7.1 months) and overall survival was 14.0 months (95% CI 10.8 months – not reached).


Orange A, et al. Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination. J Clin Oncol. 2022 Jul 22. Online ahead of print.

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