Daiichi Sankyo Company, Limited and ArQule, Inc. announced that the first patient has been enrolled in the phase III trial of ARQ 197, an investigational selective inhibitor of the c-Met receptor tyrosine kinase, in combination with erlotinib, for patients diagnosed with non-squamous, Non-Small Cell Lung Cancer (NSCLC), who have received one or two prior systemic anti-cancer therapies.

The phase III trial is a randomized, double-blinded, controlled study of previously treated patients with locally advanced or metastatic, non-squamous NSCLC who will receive ARQ 197 plus erlotinib or placebo plus erlotinib.

The primary objective is to evaluate the Overall Survival (OS) in the Intent-To-Treat (ITT) population. Secondary endpoints include OS in the subpopulation of patients with Epidermal Growth Factor Receptor (EGFR) wild type, Progression-Free Survival (PFS) in the ITT population, and further assessment of the safety of ARQ 197 in combination with erlotinib.

According to the International Agency for Research on Cancer, more than 1.6 million new cases of lung cancer were diagnosed in 2008 globally, and NSCLC accounted for 80 per cent of those cases. According to the American Cancer Society more than 220,000 cases of lung cancer will have been diagnosed in 2010 in the US. Of patients diagnosed with lung cancer in Europe, almost 90 per cent die of the disease. “With lung cancer accounting for more deaths than colon, breast and prostate cancers combined, we are very pleased to begin this phase III trial to advance the knowledge about the role ARQ 197 might have in the treatment of patients with non-small cell lung cancer in combination with erlotinib,” said Dr Kazunori Hirokawa, global head of R&D Unit, Daiichi Sankyo.

“It is our hope and expectation that this late-stage study will confirm the results we observed in patients with non-squamous cell histology in phase II, which showed promise toward extending overall survival and progression-free survival in this group when ARQ 197 was combined with erlotinib” he added.

“The start of this phase III trial marks a key milestone in the development of ARQ 197 and our partnership with Daiichi Sankyo,” said Paolo Pucci, chief executive officer of ArQule. “Lung cancer is a devastating disease, and our hope is that ARQ 197 will prove to be an effective treatment option that will help patients diagnosed with this disease.”

In October 2010, agreement was reached with the US Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for the phase III trial comparing ARQ 197 plus erlotinib against erlotinib plus placebo.

ARQ 197 is an orally available, selective inhibitor of c-Met, a receptor tyrosine kinase that is currently in phase II and phase III clinical trials and is not yet approved for use. In healthy adult cells, c-Met is present in normal levels to support natural cellular function, but in cancer cells, c-Met is inappropriately and continuously activated for unknown reasons. When abnormally activated, c-Met plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis.

Pre-clinical data have demonstrated that ARQ 197 inhibits c-Met activation in a range of human tumour cell lines and shows anti-tumour activity against several human tumour xenografts. In clinical trials to date, treatment with ARQ 197 has been well-tolerated and has resulted in tumour responses and prolonged stable disease across a broad range of tumours.

In December 2008, ArQule and Daiichi Sankyo signed a license, co-development and co-commercialization agreement to co-develop ARQ 197 in the US, Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan, where Kyowa Hakko Kirin Co., Ltd. has exclusive rights for development and commercialization.

The Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical products to address the diversified, unmet medical needs of patients in both mature and emerging markets. While maintaining its portfolio of marketed pharmaceuticals for hypertension, hyperlipidemia, and bacterial infections, the Group is engaged in the development of treatments for thrombotic disorders and focused on the discovery of novel oncology and cardiovascular-metabolic therapies.

ArQule is a biotechnology company engaged in the research and development of next generation, small-molecule cancer therapeutics. The Company’s targeted, broad spectrum products and research programs are focused on key biological processes that are central to human cancers. ArQule’s lead product, in phase II and phase III clinical development, is ARQ 197, an inhibitor of the c-Met receptor tyrosine kinase.