There is no available effective systemic treatment for patients with advanced 
hepatocellular carcinoma (HCC) who are intolerant of sorafenib or who have 
disease that has progressed on sorafenib. In Phase I and II studies, tivantinib 
(ARQ 197), an oral inhibitor of MET, demonstrated promising antitumor activity 
in patients with HCC, both as monotherapy and in combination with sorafenib. A 
randomized Phase II trial in second-line HCC showed improved overall survival 
(hazard ratio: 0.38; p = 0.01) in patients with MET-high tumors, as demonstrated 
by immunohistochemistry, treated with tivantinib versus placebo. Here we present 
the treatment rationale and study design of the METIV-HCC Phase III study. This 
randomized, double-blind study will investigate tivantinib monotherapy as 
second-line treatment in patients with advanced, pretreated, MET-high HCC. 
Approximately 303 patients will be randomized 2:1 to tivantinib or placebo for 
the purpose of analyzing the primary end point. Tivantinib will be dosed at 120 
mg twice daily, and treatment will continue until disease progression, 
unacceptable toxicity, patient or physician decision to discontinue, or death. 
The primary end point of this study is overall survival, while secondary end 
points include progression-free survival and safety. All patients will be tested 
for biomarkers. If the primary objective is achieved, this study will provide 
the first effective therapy for a biologically selected patient population in 
HCC.