Lenvatinib plus everolimus or pembrolizumab versus sunitinib in advanced renal cell carcinoma: study design and rationale

Viktor Grünwald, Thomas Powles, Toni K Choueiri, Thomas E Hutson, Camillo Porta, Masatoshi Eto, Cora N Sternberg, Sun Young Rha, Cixin S He, Corina E Dutcus, Alan Smith, Lea Dutta, Kalgi Mody, Robert J Motzer

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)929-941
Number of pages13
JournalFuture Oncology
Issue number9
Publication statusPublished - Mar 2019



  • Adult
  • Antibodies, Monoclonal, Humanized/pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics
  • Biomarkers, Tumor/analysis
  • Carcinoma, Renal Cell/drug therapy
  • Clinical Trials, Phase III as Topic
  • Everolimus/pharmacokinetics
  • Female
  • Humans
  • Kidney Neoplasms/drug therapy
  • Male
  • Multicenter Studies as Topic
  • Phenylurea Compounds/pharmacokinetics
  • Progression-Free Survival
  • Quality of Life
  • Quinolines/pharmacokinetics
  • Randomized Controlled Trials as Topic
  • Sunitinib/pharmacokinetics
  • Survival Analysis
  • Young Adult

Cite this

Grünwald, V., Powles, T., Choueiri, T. K., Hutson, T. E., Porta, C., Eto, M., Sternberg, C. N., Rha, S. Y., He, C. S., Dutcus, C. E., Smith, A., Dutta, L., Mody, K., & Motzer, R. J. (2019). Lenvatinib plus everolimus or pembrolizumab versus sunitinib in advanced renal cell carcinoma: study design and rationale. Future Oncology, 15(9), 929-941. https://doi.org/10.2217/fon-2018-0745