**3.5. HGF/MET inhibitors—rilotumumab and onartuzumab**

A number of inhibitors of the HGF/MET pathway have been developed, including monoclonal antibodies, such as rilotumumab and onartuzumab, or small molecule RTK inhibitor such as foretinib.

Rilotumumab, a humanized monoclonal antibody against HGF, has been investigated by two first-line RCTs. RILOMET-1 is a comparison between rilotumumab plus ECX (epirubicin, cisplatin and capecitabine) and a placebo plus ECX [87], and RILOMET-2 aims to evaluate cisplatin plus capecitabine with or without rilotumumab [88]. A rilotumumab benefit was seen in MET-positive patients [89] or was rilotumumab concentration dependent [90]. A very recent pharmacokinetic study revealed a lack of drug-drug interaction between rilotumumab and ECX [91]; however, the results were negative, thereby recommending the early cessation of the RILOMET-1 study [87]. Onartuzumab is a recombinant, fully humanized, monoclonal anti-MET antibody. A randomized phase II study of FOLFOX with or without onartuzumab failed to gain positive results with regard to mPFS and mOS [92]. Foretinib, an oral small molecule multikinase inhibitor that targets MET and VEGFR-2, has been evaluated by a phase II study; however, the results are discouraging [93].
