Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, ¡°Eisai¡±) announced today the initiation of a global Phase III Clinical Study (Study 307, CLEAR Study) of its in-house developed multiple receptor tyrosine kinase inhibitor lenvatinib mesylate (lenvatinib) in respective combination regimens with the anticancer agent everolimus and the anti-PD-1 antibody pembrolizumab as a potential first-line treatment for advanced renal cell carcinoma.

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 a multicenter, randomized, open-label Phase III clinical study to compare the efficacy and safety of lenvatinib/everolimus and lenvatinib/pembrolizumab versus sunitinib alone in first-line treatment in patients with advanced renal cell carcinoma. The primary outcome measure will be progression-free survival.

Non-clinical research into the combination of lenvatinib and everolimus suggested synergistic enhancement of antiangiogenic activity and a stronger antitumor effect than either monotherapy in renal cell carcinoma models through the respective inhibition of signaling pathways which facilitate tumor angiogenesis, upstream (vascular endothelial growth factor receptor [VEGFR] and fibroblast growth factor receptor [FGFR]) with lenvatinib and downstream (mammalian target of rapamycin [mTOR]) with everolimus. Furthermore, non-clinical research into the combination of lenvatinib and anti-PD-1 antibody suggested that the combination has a mechanism of action in which lenvatinib enhances the antitumor activity of the anti-PD-1 antibody by reducing immunosuppressive cells.

The number of patients with renal cancer is estimated to be approximately 338,000 worldwide, including approximately 115,000 in Europe, 58,000 in the United States and 17,000 in Japan. Renal cell carcinoma comprises more than 90% of all malignancies of the kidney, and occurs when malignant cells are found in the lining of the tubules of the kidney. The incidence of renal cell carcinoma in people over 55 years of age is rising, and it is more likely to affect men than women. For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment is molecular targeted drug therapy, however with low 5-year survival rates, this remains a disease with significant unmet medical need.

Currently lenvatinib has been approved in over 45 countries including the United States, Japan and in Europe as a treatment for refractory thyroid cancer. In May 2016, lenvatinib was approved in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy by the U.S. Food and Drug Administration in the United States. Furthermore, lenvatinib was approved in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma following one prior vascular endothelial growth factor targeted therapy in Europe in August 2016.

Eisai regards oncology as a key therapeutic area and is aiming to discover revolutionary new medicines with the potential to cure cancer. Eisai remains committed to providing further clinical evidence for lenvatinib aimed at maximizing value of the drug as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.