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ºÚÁÏÍø., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “ºÚÁÏÍø”) announced today the latest results of an additional exploratory analysis of a Phase Ⅱ clinical trial (Study 703) of its in-house developed anticancer agent lenvatinib mesylate (brand name in the U.S.: Lenvima™, “lenvatinib”) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had failed at least two systemic anticancer regimens.

Study 703 is a Phase Ⅱ, randomized, double-blind, placebo-controlled study of lenvatinib in patients with locally advanced or metastatic, non-squamous, NSCLC who had failed at least two systemic anticancer regimens. The study enrolled 135 patients who were randomized in a 2:1 ratio to receive orally either lenvatinib (24 mg) or placebo once-daily in addition to best supportive care.

According to primary analysis of the study (67% of registered patients having experienced an OS event), lenvatinib exhibited a trend of extension in OS compared to placebo (p=0.065; median OS in the lenvatinib group: 38.4 weeks, median OS in the placebo group: 24.1 weeks; Hazard Ratio 0.7 [95% CI: 0.45-1.03]), and these results were presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in 2014¹. Survival information continued to be followed and an additional exploratory analysis of OS (90% of registered patients having experienced an OS event) was recently completed. The results of the exploratory analysis generated consistent outcomes with those from the primary analysis. The lenvatinib group maintained a similar trend of extension in OS compared to placebo (nominal p-value=0.029). The most common treatment-related adverse events reported in the lenvatinib group were hypertension, proteinuria, decreased appetite, stomatitis and diarrhea.

Lung cancer is the leading cause of cancer-related mortality in both men and women, with 1.8 million new cases diagnosed every year and 1.6 million deaths reported annually worldwide. NSCLC accounts for approximately 85% of all lung cancer cases. As there is no approved standard treatment for advanced NSCLC in a third-line or greater setting, development of an effective new treatment is needed. ºÚÁÏÍø will utilize the outcome from this study to design its lenvatinib development strategy for NSCLC upon consultation with regulatory authorities.

Lenvatinib is an oral molecular targeted agent that selectively inhibits the activities of several different molecules including VEGFR, FGFR, RET, KIT and PDGFR. In particular, lenvatinib possesses a new binding mode (Type Ⅴ) to VEGFR2, as confirmed through X-ray crystal structural analysis, and exhibits rapid and potent inhibition of kinase activity, according to kinetic analysis².

Lenvatinib was approved in the United States on February 13 as Lenvima, indicated for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer. In addition, ºÚÁÏÍø has already submitted regulatory applications for lenvatinib seeking indication approval for refractory thyroid cancer to health authorities in Japan and the EU, and is filing subsequent applications in other countries worldwide. Meanwhile, ºÚÁÏÍø is also conducting a global Phase Ⅲ trial of lenvatinib in hepatocellular carcinoma as well as Phase Ⅱ studies of lenvatinib in several other tumor types.

ºÚÁÏÍø is committed to exploring the potential clinical benefits of lenvatinib in order to further contribute to patients with cancer and their families.

Kinase inhibitors are categorized into several types (Type Ⅰ to Type Ⅴ) depending on the binding site and the conformation of the targeted kinase in complex with them. Most of the currently approved tyrosine kinase inhibitors are either Type Ⅰ or Type Ⅱ, however according to X-ray crystal structural analysis, lenvatinib was found to possess a new Type Ⅴ binding mode of kinase inhibition that is distinct from existing compounds. In addition, lenvatinib was confirmed via kinetic analysis to exhibit rapid and potent inhibition of kinase activity, and it is suggested that this may be attributed to its novel binding mode.

Lung cancer is the leading cause of cancer-related mortality in both men and women, with 1.8 million new cases diagnosed every year and 1.6 million deaths reported annually worldwide. The majority of lung cancers are related to smoking, and regional incidence variations directly reflect smoking prevalence. NSCLC accounts for approximately 85% of all lung cancer cases, and the major histopathological subtypes are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Whilst surgery remains the single most consistent curative option for patients with NSCLC, many patients present with advanced disease, having metastases at the time of diagnosis which are not amenable to surgery. As there is no approved standard treatment for advanced NSCLC in a third-line or greater setting, development of an effective new treatment is needed and therefore it remains a disease with significant unmet medical needs.