ArQule and Daiichi Sankyo Announce Completion of Accrual in METIV-HCC Phase 3 Trial of Tivantinib for Second-Line Hepatocellular Carcinoma

On December 10, 2015 ArQule, Inc. (Nasdaq: ARQL) and Daiichi Sankyo, Inc. reported that the phase 3 METIV-HCC trial for tivantinib in second-line hepatocellular carcinoma (HCC) has completed accrual (Press release, ArQule, DEC 10, 2015, View Source [SID:1234508521]).

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In addition, the planned interim analysis, which is triggered when 60 percent of events occur, is expected to take place early in the second quarter of 2016.

The METIV-HCC trial is a biomarker-driven, double-blind, placebo-controlled, pivotal phase 3 trial where patients are randomized 2:1 comparing tivantinib to best supportive care. The trial is conducted under a Special Protocol Assessment and has accrued more than 300 HCC patients with MET-high tumors only, as determined by an immunohistochemistry test. The trial is being conducted in western countries by Daiichi Sankyo and ArQule with a primary endpoint of overall survival. The planned interim analysis for Data Monitoring Committee (DMC) review was designed with an early stop for superiority.

"We are pleased to have fully accrued the METIV-HCC trial prior to year-end," said Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "HCC is a disease with high unmet need and with no approved therapy for second-line treatment. It has been very encouraging to see a growing body of evidence supporting the phase 3 clinical evaluation of tivantinib in MET-high populations through a recent presentation at the International Liver Cancer Association conference."

"We would like to thank all the patients, investigators and clinical sites for partnering with us to achieve this important milestone," said Mahmoud Ghazzi, M.D., Ph.D, President and Global Head of Development for Daiichi Sankyo. "The completion of planned patient enrollment into METIV-HCC is an important step forward in the development of a potential new targeted treatment for patients with advanced HCC, who currently have limited options."

About Hepatocellular Carcinoma (HCC)
Liver cancer is the sixth most common cancer globally with 782,000 new cases in 2012 and is the second most common cause of cancer-related death with 745,000 deaths in 2012.
HCC accounts for about 90 percent of primary liver cancers. 2 Cirrhosis, chronic hepatitis B and C and smoking are recognized worldwide as factors increasing the risk of HCC.

About MET and Tivantinib (ARQ 197)
Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in phase 2 and phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth
factor receptor) antibodies such as cetuximab and panitumumab.

Pre-clinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been generally well tolerated
and has shown clinical activity in a number of tumors studied. Tivantinib has not yet been approved for any indication in any country.

In December 2008, ArQule and Daiichi Sankyo signed a license, co-development and cocommercialization agreement for tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan. In November 2015, ArQule exercised its co-commercialization option for tivantinib in the U.S. A co-commercialization agreement is expected to be finalized in the first quarter of 2016.