Abstract
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.
Keywords:
everolimus; first-line treatment; immuno-oncology; lenvatinib; pembrolizumab; renal cell carcinoma; sunitinib; tyrosine kinase inhibitor.
Publication types
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Clinical Trial Protocol
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Comparative Study
MeSH terms
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Adult
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Antibodies, Monoclonal, Humanized / pharmacokinetics
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Antibodies, Monoclonal, Humanized / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Biomarkers, Tumor / analysis*
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Carcinoma, Renal Cell / drug therapy*
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Carcinoma, Renal Cell / mortality
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Carcinoma, Renal Cell / pathology
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Clinical Trials, Phase III as Topic*
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Everolimus / pharmacokinetics
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Everolimus / therapeutic use
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Female
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Humans
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Kidney Neoplasms / drug therapy*
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Kidney Neoplasms / mortality
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Kidney Neoplasms / pathology
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Male
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Multicenter Studies as Topic
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Phenylurea Compounds / pharmacokinetics
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Phenylurea Compounds / therapeutic use
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Progression-Free Survival
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Quality of Life
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Quinolines / pharmacokinetics
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Quinolines / therapeutic use
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Randomized Controlled Trials as Topic
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Sunitinib / pharmacokinetics
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Sunitinib / therapeutic use
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Survival Analysis
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Young Adult
Substances
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Antibodies, Monoclonal, Humanized
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Biomarkers, Tumor
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Phenylurea Compounds
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Quinolines
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Everolimus
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pembrolizumab
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lenvatinib
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Sunitinib