On September 08, 2015 ArQule, Inc. (Nasdaq:ARQL) reported that additional analyses of plasma biomarkers support the prognostic and predictive role of MET status in this previously reported phase 2 trial in hepatocellular carcinoma (HCC) (Press release, ArQule, SEP 8, 2015, View Source [SID:1234507413]). The data was presented at the International Liver Cancer Association (ILCA) 9th Annual Conference on September 6th, 2015.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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 MET status as determined by immunohistochemistry emerged as the strongest predictor of tivantinib benefit. In addition, the presentation noted that biopsies were more likely to be categorized as MET-high when taken after sorafenib therapy than before therapy. The presentation can be accessed in the "Investor and Media" section of our website, www.arqule.com, under "Recent Data Presentations."
"The biomarker data from this trial demonstrates that patients with MET-high tumors are more likely to benefit from tivantinib therapy," said Dr. Brian Schwartz, head of research and development at ArQule. "On the basis of the results from the phase 2 trial and in partnership with Daiichi Sankyo, we are conducting the pivotal phase 3 METIV-HCC trial that is enrolling MET-high HCC patients as determined by a required companion diagnostic test."
By the end of 2015 the pivotal phase 3 trial, METIV-HCC, is expected to complete enrollment of approximately 300 patients, randomized 2:1 treatment to best supportive care, with the primary end-point of overall survival.
About hepatocellular carcinoma (HCC)
Globally, liver cancer is the sixth most common cancer according to the World Cancer Research Fund International (782,000 new cases in 2012) and is the second cause of cancer related death (746,000 deaths in 2012). HCC accounts for about 90 percent of primary liver cancers. 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 the 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.