“These findings represent the first randomized data reported with a c-Met inhibitor administered as a single agent in HCC,” noted ArQule chief medical officer Brian Schwartz, MD, in the announcement, highlighting results of a study exploring the safety and efficacy of tivantinib in patients who stopped responding favorably to approved liver cancer therapies.
“Second line treatment for HCC remains a challenge, lacking an approved agent,” Schwartz added. “We look forward to presenting complete data from this trial at a peer-reviewed forum later this year.”
Tivantinib, also known as ARQ 197, is designed to block the activity of a molecule known as c-Met, a member of a class of enzymes known as receptor tyrosine kinases (RTKs). RTKs have been found to play multiple key roles in human cancer, including cancer cell growth, survival, the formation of blood vessels to feed tumors (angiogenesis), organ invasion and eventual spread of the disease (metastasis).
The Phase II clinical trial of tivantinib conducted by ArQule enrolled 107 participants with inoperable liver cancer, all of whom experienced disease progression while using approved first-line options or were unable to tolerate treatment.
At the start of the study, the patients were randomized to receive tivantinib at 360 milligrams (mg), twice daily, or a placebo. However, because of high rates of neutropenia—drops in a key group of white blood cells—all tivantinib doses were reduced to 240 mg twice daily.
The study’s primary goal, or endpoint, was to confirm tivantinib therapy was associated with a slower time to liver cancer progression, compared with placebo. Though data from the study have not yet been publicly presented or reported in a peer-reviewed medical journal, ArQule said this primary endpoint was met, with a 64 percent chance of cancer progression among those receiving placebo, compared with 56 percent of the tivantinib recipients.
This difference was statistically significant, meaning that it was too great to have occurred by chance.
Side effects were reported at similar rates in the treatment and placebo groups, with the exceptions of higher rates of fatigue and bone marrow abnormalities—notably neutropenia and anemia—among those receiving tivantinib.
ArQule notes that HCC is the most common primary cancer of the liver. The incidence is increasing, and HCC has risen to become the fifth most common malignancy worldwide and the third leading cause of cancer-related death, exceeded only by cancers of the lung and stomach.
There are about 500,000 to 1 million new cases of HCC annually, causing 600,000 deaths globally per year. Chronic hepatitis B and C—along with cirrhosis of the liver—are recognized as the major factors worldwide increasing the risk of liver cancer.