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

doi:10.2217/fon-2018-0745

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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

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.

Original language	English
Pages (from-to)	929-941
Number of pages	13
Journal	Future Oncology
Volume	15
Issue number	9
DOIs	https://doi.org/10.2217/fon-2018-0745
Publication status	Published - 2019 Mar

Bibliographical note

Funding 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.

Funding Information:
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.

Funding Information:
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.

Publisher Copyright:
© 2019 Future Medicine Ltd.

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following Sustainable Development Goal(s)

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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

Grünwald, Viktor ; Powles, Thomas ; Choueiri, Toni K. ; Hutson, Thomas E. ; Porta, Camillo ; Eto, Masatoshi ; Sternberg, Cora N. ; Rha, Sun Young ; He, Cixin S. ; Dutcus, Corina E. ; Smith, Alan ; Dutta, Lea ; Mody, Kalgi ; Motzer, Robert J. / Lenvatinib plus everolimus or pembrolizumab versus sunitinib in advanced renal cell carcinoma : Study design and rationale. In: Future Oncology. 2019 ; Vol. 15, No. 9. pp. 929-941.

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title = "Lenvatinib plus everolimus or pembrolizumab versus sunitinib in advanced renal cell carcinoma: Study design and rationale",

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.",

author = "Viktor Gr{\"u}nwald and Thomas Powles and Choueiri, {Toni K.} and Hutson, {Thomas E.} and Camillo Porta and Masatoshi Eto and Sternberg, {Cora N.} and Rha, {Sun Young} and He, {Cixin S.} and Dutcus, {Corina E.} and Alan Smith and Lea Dutta and Kalgi Mody and Motzer, {Robert J.}",

note = "Funding 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. Funding Information: 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. Funding Information: V Gr{\"u}nwald 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. Publisher Copyright: {\textcopyright} 2019 Future Medicine Ltd.",

year = "2019",

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language = "English",

volume = "15",

pages = "929--941",

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Lenvatinib plus everolimus or pembrolizumab versus sunitinib in advanced renal cell carcinoma : Study design and rationale. / Grünwald, Viktor; Powles, Thomas; Choueiri, Toni K.; Hutson, Thomas E.; Porta, Camillo; Eto, Masatoshi; Sternberg, Cora N.; Rha, Sun Young; He, Cixin S.; Dutcus, Corina E.; Smith, Alan; Dutta, Lea; Mody, Kalgi; Motzer, Robert J.

In: Future Oncology, Vol. 15, No. 9, 03.2019, p. 929-941.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Lenvatinib plus everolimus or pembrolizumab versus sunitinib in advanced renal cell carcinoma

T2 - Study design and rationale

AU - Grünwald, Viktor

AU - Powles, Thomas

AU - Choueiri, Toni K.

AU - Hutson, Thomas E.

AU - Porta, Camillo

AU - Eto, Masatoshi

AU - Sternberg, Cora N.

AU - Rha, Sun Young

AU - He, Cixin S.

AU - Dutcus, Corina E.

AU - Smith, Alan

AU - Dutta, Lea

AU - Mody, Kalgi

AU - Motzer, Robert J.

N1 - Funding 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. Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2019 Future Medicine Ltd.

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

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U2 - 10.2217/fon-2018-0745

DO - 10.2217/fon-2018-0745

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AN - SCOPUS:85063201714

VL - 15

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JO - Future Oncology

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SN - 1479-6694

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ER -

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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