CLEAR Trial: Lenvatinib Plus Pembrolizumab in Advanced Renal Cell Carcinoma


Robert J. Motzer, MD, provides an overview of the CLEAR trial investigating lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma.


Robert J. Motzer, MD: The CLEAR trial [NCT02811861] is a randomized phase 3 study in first-line therapy for patients with clear cell RCC [renal cell carcinoma] that [randomly assigned] patients to [an] experimental arm of lenvatinib plus pembrolizumab compared [with] sunitinib, the standard of care, and lenvatinib plus everolimus [with] sunitinib. It was a large, randomized global 3-arm trial that compared those 2 lenvatinib-based experimental treatments [with] sunitinib, which has been the standard of care for many years. The primary end point of the trial was progression-free survival [PFS] and both of the lenvatinib-based arms met the primary end point—the lenvatinib plus pembrolizumab and lenvatinib plus everolimus. The median [PFS] for lenvatinib plus pembrolizumab was 23 months and the response rate was over 70%. Both were much better than sunitinib, and the margin for benefit was larger than that of lenvatinib plus everolimus over sunitinib. In addition, the trial met the secondary end point of an overall survival [OS] benefit for lenvatinib plus pembrolizumab compared with sunitinib. However, lenvatinib plus everolimus did not demonstrate improved [OS] compared with sunitinib, so lenvatinib plus pembrolizumab was really the winner of the trial. As a result of that, [this regimen] received regulatory approval for first-line therapy for advanced RCC.

[Regarding] the other secondary end points, safety is certainly a critical one. In general, there weren’t any new safety signals for the combination over each agent alone. There were a fairly large number of patients who required dose reductions of lenvatinib plus pembrolizumab. But the therapy was really administered for a long time, and these adverse effects were generally manageable by supportive care measures or by dose modification. As a result of that trial, lenvatinib plus pembrolizumab became an option for first-line therapy for patients with advanced [RCC].

Transcript is AI-generated and edited for clarity and readability.

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