Phase 2 Study Update of Tivantinib for Hepatocellular Carcinoma

ArQule and Daiichi Sankyo announced final results from a randomized, placebo-controlled, double-blind, Phase 2 clinical of tivantinib as a single-agent, investigational, second-line treatment in hepatocellular carcinoma (HCC).

The 107 patients in the trial had unresectable HCC and had disease progression after first-line therapy or were unable to tolerate the first-line therapy. Patients were randomized to receive tivantinib at 360mg twice daily or 240mg twice daily or placebo (2:1 tivantinib:placebo). The primary endpoint was time to progression (TTP) in the intent to treat (ITT) population. Other study endpoints were disease control rate (DCR), progression free survival (PFS), overall survival (OS), as well as safety for the ITT population and pre-defined MET-high or MET-low cohorts (as defined by immunohistochemistry).

A statistically significant 56% improvement as compared to placebo was seen in TTP in the ITT population (hazard ratio [HR]=0.64; 90% confidence intervals [CI]=0.43–0.94; log rank P-value=0.04). The median TTP in tivantinib arm was 1.6 months and 1.4 months in the placebo arm. There was no significant difference in TTP or OS between tivantinib and placebo in the MET-low cohorts. In the MET-high cohort, there were statistically significant improvements in TTP, PFS and OS:

- Median OS in tivantinib arm was 7.2 months and 3.8 months in the placebo arm (HR=0.38; 95% CI=0.18–0.81; log rank P-value=0.01)

- Median TTP was 2.9 months in the tivantinib arm and 1.5 months in the placebo arm (HR=0.43; 95% CI=0.19–0.97; log rank P-value=0.03)

- Median PFS was 2.4 months in the tivantinib arm and 1.5 months in the placebo arm (HR=0.45; 95% CI=0.21–0.95; log rank P-value=0.02).

Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase. When abnormally activated in cancer cells, MET plays roles in cell growth, survival, angiogenesis, invasion and metastasis.

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