Regulatory Decision Summary for Lenvima

The safety and efficacy of lenvatinib in combination with everolimus for the treatment of patients with advanced RCC after one prior vascular endothelial growth factor (VEGF)-targeted therapy were investigated during the Phase 2 portion of the pivotal Phase 1b/2 Study 205, a randomized, controlled, open-label trial.

The primary efficacy endpoint was investigator-assessed Progression-Free Survival (PFS). Results showed that the combination (lenvatinib 18 mg with everolimus 5 mg) significantly prolonged investigator-assessed PFS compared to everolimus monotherapy (10 mg). Key secondary endpoints included overall survival (OS) and objective response rate (ORR). The results from these endpoints were consistent with the PFS benefit. Although the efficacy results stemmed from a Phase 2 trial conducted in a small number of patients, the PFS and ORR gains are robust for the second-line setting and are clinically meaningful.

Adverse events that were observed with the combination are in line with the known safety profile of lenvatinib. There were no new adverse events identified in Study 205. Four adverse events occurred at a greater frequency with the combination (lenvatinib + everolimus) are diarrhea, hypercholesterolemia, hypothyroidism and increased blood TSH.

Lenvatinib in combination with everolimus has demonstrated clinically significant benefits in patients with advanced RCC who have received one prior VEGFR-targeted therapy. The overall benefits of lenvatinib in combination with everolimus are considered to outweigh the risks.