Tivantinib in hepatocellular carcinoma

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Tivantinib (ARQ 197) is an oral, selective MET receptor tyrosine kinase inhibitor.
• Preclinical studies demonstrated broad-spectrum antitumor activity, particularly in MET-overexpressing cell lines.

Purpose of the Study:

• To review preclinical data, Phase I/II studies of tivantinib in advanced hepatocellular carcinoma (HCC).
• To analyze MET expression as a companion diagnostic and assess tivantinib's safety profile in HCC.

Main Methods:

• Review of preclinical data, Phase I monotherapy/combination studies (with sorafenib), and a Phase II HCC study.
• Analysis of MET expression as a predictive biomarker.
• Evaluation of tivantinib's safety and efficacy in advanced HCC.

Main Results:

• Tivantinib demonstrated significant improvements in progression-free and overall survival in MET-high HCC patients compared to placebo in a Phase II study.
• Combination therapy with sorafenib showed promising activity.
• Adverse events included hematological toxicity, asthenia, and appetite loss, leading to dose adjustments.

Conclusions:

• Tivantinib, an ATP-independent MET inhibitor, disrupts MET signaling and shows efficacy in MET-high advanced HCC.
• MET overexpression is a negative prognostic factor in HCC post-sorafenib.
• A pivotal Phase III trial in advanced, MET-high HCC is planned.