The following is a summary of “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,” published in the January 2023 issue of Oncology by Arance, et al.

Melanoma that advances on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1) requires effective therapy. Therefore, for a study, researchers carried out phase II LEAP-004 research to assess the effectiveness of the combination of the PD-1 inhibitor pembrolizumab with the multikinase inhibitor lenvatinib.

Lenvatinib 20 mg orally once daily plus approximately ≤35 doses of pembrolizumab 200 mg intravenously once every 3 weeks were given to eligible patients with unresectable stage III–IV melanoma who had confirmed progressive disease (PD) within 12 weeks of the last dose of a PD-1/L1 inhibitor, alone or in combination with other therapies, including cytotoxic T-cell lymphocyte–associated antigen 4 (CTLA-4) inhibitors. The treatment was continued until PD or unacceptable toxicity. The objective response rate (ORR), according to RECIST, version 1.1, by independent central review, was the main outcome measure.

About 103 patients in all were enrolled and received care. 15.3 months was the average study follow-up period. With 3 (2.9%) complete replies and 19 (18.4%) partial responses, the ORR for the entire population was 21.4% (95% CI, 13.9 to 30.5). The median response time was 8.3 months (3.2–15.9+). In the 30 patients with PD who had previously had anti-PD-1 and anti-CTLA-4 treatment, ORR was 33.3%. In the whole population, the median progression-free survival and overall survival were, respectively, 4.2 months (95% CI, 3.8 to 7.1) and 14.0 months (95% CI, 10.8 to not attained). Around 47 (45.6%) patients experienced grade 3-5 treatment-related adverse events, the most prevalent of which was hypertension (21.4%); one patient passed away as a result of a treatment-related incident (decreased platelet count). 

In advanced melanoma patients with proven PD on prior PD-1/L1 inhibitor-based treatment, including those with PD on anti-PD-1 + anti-CTLA-4 therapy, lenvatinib with pembrolizumab produced clinically significant, long-lasting responses. The safety profile matched predictions. The results supported the prospective combination of lenvatinib + pembrolizumab for the group with a high unmet need.

Referencee: ascopubs.org/doi/full/10.1200/JCO.22.00221