Daiichi Sankyo Company Limited, and ArQule, Inc., a biotechnology company engaged in the research and development of next-generation, small-molecule cancer therapeutics, have enrolled the first patient in the pivotal phase 3 METIV-HCC (MET-high patients with tivantinib in HCC) trial of tivantinib (ARQ 197).

Tivantinib, an investigational selective inhibitor of MET, a receptor tyrosine kinase, is being evaluated for the treatment of patients diagnosed with hepatocellular carcinoma (HCC) who have received one or two prior systemic anti-cancer therapies.

The METIV-HCC trial is a randomized, double-blinded, controlled study of previously treated patients with MET-high inoperable HCC who will receive tivantinib or placebo. The primary endpoint is overall survival (OS), and the secondary endpoint is progression-free survival (PFS). Approximately 300 patients are planned to be enrolled at approximately 120 clinical centres worldwide.

"We are very pleased to begin this phase 3 trial to advance our understanding of the potential role of tivantinib in the treatment of HCC," said Glenn Gormley, global head of research and development and senior executive officer, Daiichi Sankyo. "It is our hope that this late-stage study will confirm the positive results we saw in phase 2 in time to progression (TTP) and overall survival (OS) observed in patients whose tumours were MET-high."

"Hepatocellular carcinoma is a devastating disease, and patients with advanced HCC are in need of new therapies that can help extend their lives," said Paolo Pucci, chief executive officer of ArQule. "The METIV-HCC trial follows positive Phase 2 results that demonstrated improvements in overall survival and time to progression observed among MET-high patients."

In October 2012, agreement was reached with the US Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for this pivotal Phase 3 trial. The SPA process is a procedure by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols that are intended to form the basis for a New Drug Application. Final marketing approval depends on the results of the trial.

Globally, liver cancer is the sixth most common cancer (749,000 new cases), accounting for 7 per cent of all cancers, and is the third leading cause of cancer related death (692,000 cases).1 HCC represents more than 90 percent of primary liver cancers.2 Chronic hepatitis B and C are recognized as the major factors worldwide increasing the risk of HCC, with risk being even greater in the presence of co-infection with these viruses.3 Cirrhosis is also a risk factor for development of HCC.

Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase. Tivantinib is currently in phase 3 development and has not been approved in any market. In healthy adult cells, MET is present in normal levels to support natural cellular function, but in cancer cells MET is inappropriately and continuously activated for unknown reasons. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis.

In December 2008, ArQule and Daiichi Sankyo signed a license, co-development and co-commercialization agreement for tivantinib (ARQ 197) in the US, Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan.

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.