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Press Release

Now Enrolling: Global Phase 3 Clinical Trial to Evaluate Potential First-Line Use of Lenvatinib in Combination with Pembrolizumab or Everolimus for Patients with Advanced Renal Cell Carcinoma

Posted on: 30 Sep 16

WOODCLIFF LAKE, N.J., Sept. 29, 2016 /PRNewswire/ -- Eisai Inc. announced today the initiation of a multicenter, global, randomized Phase 3 study that will evaluate the efficacy and safety of two regimens containing Eisai's multiple receptor tyrosine kinase inhibitor lenvatinib, marketed in the U.S. as LENVIMA® – lenvatinib in combination with the anti-PD-1 immunotherapy pembrolizumab, marketed under the brand name KEYTRUDA® by Merck & Co. Inc., known as MSD outside of the U.S. and Canada, and lenvatinib in combination with everolimus (LEN+EVE) – versus sunitinib in patients with advanced renal cell carcinoma (RCC) in the first-line setting. The CLEAR (Comparison of the efficacy and safety of Lenvatinib in combination with Everolimus or pembrolizumab versus sunitinib alone in first-line treatment of subjects with Advanced Renal cell carcinoma) study is designed to assess the potential of these combinations to extend progression-free survival (PFS) in these patients.

"Previous studies offer a strong scientific rationale for investigating these lenvatinib-based combinations as potential first-line treatments for patients with advanced renal cell carcinoma. Following the efficacy seen in the registrational trial that led to the FDA approval of the lenvatinib-everolimus combination for the treatment of advanced RCC following prior antiangiogenic therapy and results of preclinical research showing that lenvatinib enhances the anti-tumor activity of anti-PD-1 therapy, we look forward to the study of these combinations in the frontline setting for patients with advanced RCC," said Robert Motzer, MD, Memorial Sloan Kettering Cancer Center, New York, and the principal investigator of the study. "This Phase 3 study will provide a better understanding of the respective combined effects of these therapies and their potential impact on the treatment landscape for these patients."

CLEAR is the first Phase 3 trial to assess lenvatinib in combination with everolimus, an mTOR inhibitor, in the first-line setting. In May 2016, the FDA approved this combination for the treatment of patients with advanced renal cell carcinoma who were previously treated with an anti-angiogenic therapy based primarily on the results of Study 205. The approval followed a Priority Review and a Breakthrough Therapy designation. The combination of lenvatinib and everolimus showed increased anti-angiogenic and anti-tumor activity as demonstrated by decreased human endothelial cell proliferation, tube formation, and VEGF signaling in vitro and tumor volume in mouse xenograft models of human renal cell cancer greater than each drug alone.

CLEAR is also the first Phase 3 trial to assess lenvatinib in combination with pembrolizumab, an anti-PD-1 (programmed death receptor-1) immunotherapy, in previously untreated patients with advanced RCC. Preclinical studies have indicated that lenvatinib reduces the production of immune-suppressing cells and enhances the anti-tumor effect of PD-1 signal inhibitors.

"LENVIMA has the potential to play a significant role in combination regimens that aim to prolong the lives of patients with advanced cancers, a core mission for all of us at Eisai," said Alton Kremer, MD, PhD, Chief Clinical Officer and Chief Medical Officer, Oncology Business Group at Eisai. "We are committed to providing patients in need with additional treatment options, and this trial allows us to further explore the potential of LENVIMA earlier in the treatment of advanced RCC."

For more information about the CLEAR trial, please click here. Patients and investigators interested in participating in this trial should contact Eisai Medical Information at 1-888-274-2378.

This release discusses an investigational use for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval.

About the CLEAR Trial

CLEAR, a Phase 3 clinical trial, will plan to enroll 735 patients with advanced RCC who have not received any previous systemic therapy. Patients will be randomized 1:1:1 to receive a combination of lenvatinib (20 mg orally, once daily) plus pembrolizumab (200 mg intravenously, every 3 weeks); lenvatinib (18 mg orally, once daily) plus everolimus (5 mg orally, once daily); or sunitinib (50 mg orally, once daily, on a schedule of four weeks on treatment followed by two weeks off treatment). The primary endpoint of this study is PFS; other endpoints include objective response rate (ORR), overall survival (OS) and safety. 

About Study 205, the Registrational, Second-line Advanced Renal Cell Carcinoma Trial

Study 205 was a multicenter, randomized Phase 2 trial in patients (n=153) with unresectable advanced or metastatic RCC who were previously treated with an anti-angiogenic therapy and randomized 1:1:1 to receive a combination of 18 mg lenvatinib plus 5 mg everolimus, lenvatinib only (24 mg) or everolimus only (10 mg) administered orally once a day in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary efficacy endpoint of this study was investigator-assessed PFS and other endpoints of the study included ORR, OS and safety.

About Renal Cell Carcinoma

Renal cell carcinoma (RCC), also known as renal cell cancer or renal cell adenocarcinoma, is the most common type of kidney cancer, representing about 90% of cases in the United States. Renal cell carcinoma occurs when malignant cells are found in the lining of the tubules in the kidney. While RCC usually grows as a single tumor within a kidney, there may also be two or more tumors in one or both kidneys. In 2016, it is estimated that there will be approximately 62,700 new cases of kidney cancer, and about 14,240 people will die from the disease. Approximately 16% of patients with RCC will have metastases at diagnosis, and as many as 40% will demonstrate metastasis after primary surgical treatment for localized RCC. With a 5-year survival rate ranging from 5% to 12%, the prognosis for these patients is poor.

About LENVIMA® (lenvatinib)

LENVIMA® (lenvatinib) is a kinase inhibitor that is indicated for:

Differentiated Thyroid Cancer (DTC): single agent for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC.

Renal Cell Cancer (RCC): in combination with everolimus for patients with advanced RCC following one prior anti-angiogenic therapy.

Lenvatinib, discovered and developed by Eisai, is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3. Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.

Editor's Details

Mike Wood

Last updated on: 30/09/2016

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