Aim: Lenvatinib plus everolimus is approved for the treatment of advanced renal cell carcinoma (RCC) after one prior vascular endothelial growth factor-targeted therapy. Lenvatinib plus pembrolizumab demonstrated promising antitumor activity in a Phase I/II trial of RCC. Methods: We describe the rationale and design of the CLEAR study, a three-arm Phase III trial comparing lenvatinib plus everolimus and lenvatinib plus pembrolizumab versus sunitinib monotherapy for first-line treatment of RCC. Eligible patients must have advanced clear cell RCC and must not have received any prior systemic anticancer therapy. The primary end point is progression-free survival; secondary end points include objective response rate, overall survival, safety, health-related quality of life and pharmacokinetics. Biomarker evaluations are included as exploratory end points.
Bibliographical noteFunding Information:
Here, we describe the design and rationale of the CLEAR study (NCT02811861; EudraCT 2016-000916-14), a multicenter, randomized, open-label and Phase III trial, designed to evaluate whether the combination of two targeted therapies (lenvatinib plus everolimus) or the combination of one targeted therapy plus a PD-1 inhibitor (lenvatinib plus pembrolizumab) would be superior to standard first-line therapy with single-agent sunitinib in patients with advanced or metastatic RCC. The study is funded by Eisai Inc., with study support also provided by Merck & Co., Inc.
This study is funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck & Co., Inc., Kenilworth, NJ, USA. Editorial support with the preparation of this manuscript was provided by Marcel Kuttab, PharmD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, with funding provided by Eisai Inc.
V Grünwald reports grants, personal fees and nonfinancial support from Bristol-Myers Squibb, Merck Sharp & Dohme and Novartis; personal fees and nonfinancial support from Roche and Ipsen; grants and personal fees from AstraZeneca and Pfizer; and personal fees from Eisai, EUSA Pharma and Cerulean.
All Science Journal Classification (ASJC) codes
- Cancer Research