Tivantinib is an investigational oral inhibitor of the MET receptor tyrosine kinase currently in phase 3 clinical development for the second-line treatment of hepatocellular carcinoma (HCC), the most common type of primary liver cancer. Randomized, placebo-controlled clinical trials have shown activity of tivantinib in patients with several tumor types and high tumor MET expression by immunohistochemistry. Orphan Drug Designation for HCC was granted by the US Food and Drug Administration (FDA) and the European Commission in 2013.
Tivantinib is being jointly developed by ArQule and Daiichi Sankyo in the Americas, Europe, Australia and rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan, where development is being conducted by ArQule and Kyowa-Hakko Kirin.
Our most advanced trial with tivantinib, METIV-HCC, was a pivotal Phase 3 randomized, double-blind, controlled study of tivantinib as single agent therapy in previously treated patients with MET diagnostic-high, inoperable HCC conducted by Daiichi Sankyo and us. The primary endpoint was overall survival (OS) in the intent-to-treat (ITT) population, and the secondary endpoint was progression-free survival (PFS) in the same population. On February 17, 2017, we and Daiichi Sankyo announced that the METIV-HCC trial did not meet its primary endpoint of improving OS.
A second Phase 3 clinical trial with tivantinib known as JET-HCC is ongoing in Japan. JET-HCC is a pivotal, randomized, double-blind, controlled study of tivantinib as single-agent therapy in previously treated patients with MET diagnostic-high, inoperable HCC conducted by Kyowa Hakko Kirin. The primary endpoint is PFS in the ITT population. Kyowa Hakko Kirin has enrolled approximately 190 patients in the study. We expect to receive final results of this study in late Q1 or early Q2 2017.
Overexpression of the MET pathway is associated with poor outcomes in many cancers, including HCC, non-small cell lung cancer (NSCLC) and others.
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 for unknown reasons. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis.
Hepatocellular Carcinoma (HCC)
Liver cancer is the abnormal and uncontrolled growth of cells within the liver that disrupt normal liver function. It is typically defined as either primary liver cancer, which starts in the liver, or secondary liver cancer, which spreads to the liver from another part of the body such as the pancreas, colon, stomach, breast or lung.
There are three types of primary liver cancer:
About 90% of all liver cancers are HCC. Current treatment options include surgery, tumor ablation, embolization therapy, radiation treatment, and targeted 1st line therapy (sorafenib). No standard of care exists for second-line therapy.