Tivantinib, an experimental oral inhibitor of the MET receptor, is not better than best supportive care in patients with inoperable hepatocellular carcinoma (HCC) who are intolerant or have previously received systemic therapy.
“HCC is a disease with high unmet need, especially in the second-line setting, so these results are disappointing for the patients as well as the investigators and the companies,” ArQule CEO Paolo Pucci said in a news release.
Expression of MET in tumors is associated with aggressive disease and shorter survival in patients with HCC, the most common form of liver cancer. Therefore, the Phase 3 METIV-HCC trial (NCT01755767) was designed to assess whether the MET inhibitor tivantinib could provide any survival benefit to HCC patients who exhibited high levels of this protein at the time of diagnosis.
The randomized, double-blind study enrolled 340 patients with inoperable, high-MET HCC who had received at least one prior systemic therapy. Patients were randomized to receive either twice-daily oral tivantinib (120 mg in the morning and at night with food) or a matching placebo.
The study’s primary endpoint was overall survival, and secondary outcomes included progression-free survival and safety.
The companies have now announced that the study did not meet its primary endpoint of overall survival, showing that the MET inhibitor is not superior to best supportive care in these patients.
“Despite the negative outcome of this study, we remain committed to applying rigorous science to unmet needs for patients with cancer,” said Antoine Yver, MD, MSc, executive vice president and global head, Oncology Research and Development at Daiichi Sankyo. “We would like to take this opportunity to thank all of the investigators, and especially the patients, for their participation in this study.”
According to estimates from the American Cancer Society, liver cancer incidence has more than tripled since 1980. In 2017, more than 40,000 people are expected to receive a liver cancer diagnosis in the United States, and nearly 29,000 will die from the disease. Hepatocellular carcinoma accounts for about 90 percent of all primary liver cancers. Its main risk factors are cirrhosis, chronic hepatitis B and C, and smoking.