ArQule presents additional clinical biomarker data from Phase 2 study of tivantinib in hepatocellular carcinoma

BURLINGTON, Mass.—ArQule Inc. announced in September that additional analyses of plasma biomarkers support the prognostic and predictive role of MET status in a previously reported Phase 2 trial in hepatocellular carcinoma (HCC) involving tivantinib, an orally administered, selective inhibitor of MET, a receptor tyrosine kinase.

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 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 endpoint of overall survival.

Globally, liver cancer is the sixth most common cancer (782,000 new cases in 2012) and is the second-leading cause of cancer related death (746,000 deaths in 2012). HCC accounts for about 90 percent of primary liver cancers.

Preclinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows antitumor 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.