Clinical Outcomes of Lenvatinib-Pembrolizumab in a High-Risk, Dual ICI-Refractory Melanoma Cohort.

Background: Resistance to immune checkpoint inhibitors (ICIs) remains a major therapeutic challenge in advanced melanoma. The phase II LEAP-004 trial demonstrated activity of lenvatinib plus pembrolizumab after ICI failure; however, real-world data are limited. Methods: We conducted a retrospective single-center case series of nine consecutive patients with unresectable or metastatic melanoma refractory to prior immunotherapy who received lenvatinib plus pembrolizumab. Tumor responses were assessed according to RECIST v1.1 criteria. Survival outcomes were estimated using the Kaplan-Meier method. Results: The median age was 53 years; 44% of patients had baseline brain metastases, and all tumors were BRAF wild type. The objective response rate was 22.2%, and the disease control rate was 33.3%. Median progression-free survival was 4.0 months, and median overall survival was 9.6 months. Treatment-related adverse events were generally manageable, with one patient experiencing grade 3 colitis. Conclusion: In this high-risk, dual ICI-refractory cohort, lenvatinib plus pembrolizumab showed manageable toxicity and clinical outcomes broadly consistent with previous reports. Although limited by the small sample size and retrospective design, these findings support the feasibility of this regimen in routine clinical practice and warrant further prospective evaluation.