On January 25, 2016 ArQule, Inc. (NASDAQ:ARQL) reported that an analysis of preliminary baseline tumor MET status of patients screened in the phase 3 METIV-HCC trial for tivantinib in second-line hepatocellular carcinoma (HCC) confirms previously presented data from the company’s phase 2 trial in the same patient population (Press release, ArQule, JAN 25, 2016, View Source [SID:1234508855]). In both trials MET status, as determined by immunohistochemistry, was more frequently high after first-line therapy and was a predictive and prognostic biomarker in the phase 2 trial. The data was presented in an oral presentation and poster at the 2016 Gastrointestinal Cancers Symposium (ASCO GI) on January 22, 2016. Schedule your 30 min Free 1stOncology Demo! The METIV-HCC trial screened patient tumor biopsies for MET status as an inclusion criteria for Met-high patients. Approximately half of the more than 1,000 samples tested were MET-high. A higher MET-high rate (73%) was observed in those samples from patients analyzed following first-line treatment with sorafenib while a lower MET-high rate (39%) was observed in those samples analyzed prior to sorafenib treatment.
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An additional analysis found that 70% (50 out of 71) of patients who tested MET-low before sorafenib treatment became MET-high after receiving sorafenib. The presentations can be accessed in the "Publications and Presentations" section of our website, www.arqule.com.
"The totality of the biomarker data presented further enforces our confidence in the design and target patient population that we have chosen for the METIV-HCC trial," said Dr. Brian Schwartz, Chief Medical Officer and Head of Research and Development at ArQule. "Having recently completed enrollment, we look forward to the planned interim analysis early in the second quarter."
The METIV-HCC trial, being conducted in western countries in partnership with Daiichi Sankyo, has completed enrollment and a planned interim analysis, which is triggered when 60% of events occur, is expected to take place early in the second quarter of 2016. The trial enrolled over 300 patients, is randomized 2:1 treatment to best supportive care, and has overall survival as its primary end-point.
The phase 2 study, completed in the third quarter of 2011 and published in The Lancet Oncology medical journal in November 2012, enrolled 107 HCC patients who progressed or were intolerant to one prior systemic therapy. Multiple biomarkers were evaluated as part of the study, and tumor MET status as determined by immunohistochemistry emerged as the strongest predictor of tivantinib response.
About Hepatocellular Carcinoma (HCC)
Liver cancer is the sixth most common cancer globally with about 782,000 new cases in 2012 and is the second most common cause of cancer-related death with 746,000 deaths in 2012.i HCC accounts for about 90 percent of primary liver cancers.ii Cirrhosis, chronic hepatitis B and C and smoking are recognized worldwide as factors increasing the risk of HCC.ii
About MET and Tivantinib (ARQ 197)
Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in two 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 co-commercialization 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.