Medical Oncology & Hematology Unit, Humanitas Cancer Center, Istituto Clinico Humanitas, IRCCS. Via Manzoni 56, 20089 Rozzano (Milano), Italy.
Tivantinib (ARQ 197) is an orally administered, selective small molecule that inhibits mesenchymal-epithelial transition factor (MET) via a novel, ATPindependent binding mechanism. Preclinical studies demonstrated that tivantinib has a broadspectrum anti-tumor activity, especially in cells expressing high levels of MET. A randomized Phase II study in second-line hepatocellular carcinoma showed statistically significant improvement in time to progression with tivantinib compared to a placebo. Noteworthy, a significant pronounced benefit in time to progression and overall survival was observed in METhigh patients. In addition, MET expression was defined as a negative prognostic factor. The most frequent adverse events were hematologic events. A Phase III study in the MET-high hepatocellular carcinoma is actively recruiting patients. Phase II and III studies in non-small-cell lung cancer and colorectal cancer are ongoing.