Targeting the HGF-cMET Axis in Hepatocellular Carcinoma

Table 1

HGF-cMET inhibitors in active clinical trials for HCC or solid tumors including HCC, as of March 2013.

Agent	Type	Drug targets	Phase	Patient selection	Status	NCI reference	Manufacturer
ARQ 197
Tivantinib (T); T plus sorafenib; T plus pazopanib; T plus temsirolimus; T plus topotecan	Receptor TKI: non-ATP competitive	cMET	I; I; Ib; I; I	HCC; Solid tumors; Solid tumors*; Solid tumors; Solid tumors	Recruiting; Active, not R; Recruiting; Recruiting; Recruiting	NCT01656265; NCT00827177; NCT01468922; NCT01625156; NCT01654965	Daiichi Sankyo
XL 184
Cabozantinib	Receptor TKI: ATP competitive	cMET, RET, VEGFR1-3, KIT, FLT3, and TIE2	II; II	Solid tumors; Solid tumors	Active, not R; Recruiting	NCT00940225; NCT01588821	Exelixis
INC280
Formerly INCB028060	Receptor TKI: ATP competitive	cMET	I; I; I	Solid tumors; Solid tumors*; Solid tumors	Recruiting; Recruiting; Active, not R	NCT01546428; NCT01324479; NCT01072266	Novartis; Incyte
GSK1363089
Foretinib; Formerly XL 880	Receptor TKI: ATP competitive	cMET, RON, VEGFR1-3, PDGFR, KIT, FLT3, and TIE2	I/II	HCC	Active, not R	NCT00920192	GSK
AMG 208	Receptor TKI: ATP competitive	cMET, VEGFR1-3, RON, and TIE2	I	Solid tumors	Active, not R	NCT00813384	Amgen
AMG 337	Receptor TKI: ATP competitive	cMET	I	Solid tumors	Recruiting	NCT01253707	Amgen
EMD 1214063	Receptor TKI: ATP competitive	cMET	I	Solid tumors*	Recruiting	NCT01014936	EMD Serono
PF-02341066
Crizotinib (Cr); Crizotinib; Cr plus pemetrexed or pazopanib	Receptor TKI: ATP competitive	cMET, ALK, and ROS	I; I; I	Solid tumors*; Solid tumors; Solid tumors*	Recruiting; Recruiting; Recruiting	NCT00585195; NCT01576406; NCT01548144	Pfizer
E7050
E7050; E7050 plus sorafenib	Receptor TKI: ATP competitive	cMET	I; I/II	Solid tumors; HCC	Recruiting; Recruiting	NCT01428141; NCT01271504	Eisai
MGCD-265
MGCD-265; MGCD-265 plus erlotinib or docetaxel	Receptor TKI: ATP competitive	cMET, RON, VEGFR1-2, PDGFR, KIT, FLT3, and TIE2	I; I/II	Solid tumors; Solid tumors	Recruiting; Recruiting	NCT00697632; NCT00975767	MethylGene
SAR125844	Receptor TKI: ATP competitive	cMET	I; I	Solid tumors*; Solid tumors*	Recruiting; Recruiting	NCT01391533; NCT01657214	Sanofi
ASLAN002
Formerly BMS777607	Receptor TKI: ATP competitive	cMET	I	Solid tumors	Recruiting	NCT01721148	Aslan
AV-299
Ficlatuzumab plus/minus erlotinib; Formerly SCH 900105	Ligand antagonist: monoclonal antibody	HGF	I	Solid tumors	Active, not R	NCT00725634	AVEO
LY 2875358
LY 2875358; LY 2875358 plus/minus erlotinib	Receptor inhibitor: monoclonal antibody	cMET	I; I	Solid tumors; Solid tumors	Recruiting; Recruiting	NCT01602289; NCT01287546	Eli Lilly
OPB-31121	IL-6-induced STAT3 phosphorylation inhibitor	STAT3	I/II	HCC	Recruiting	NCT01406574	Otsuka
OPB-51602	IL-6-induced STAT3 phosphorylation inhibitor	STAT3	I; I	Solid tumors; Solid tumors	Active, not R; Recruiting	NCT01423903; NCT01184807	Otsuka

^∗Inclusion criteria require evidence of cMET dysregulation for some or all patients.
Active, not R: active not recruiting; ALK: anaplastic lymphoma kinase; ATP: adenosine triphosphate; GSK: GlaxoSmithKline; HGF: hepatocyte growth factor; HCC: hepatocellular carcinoma; IL6: interleukin-6; PDGFR: platelet-derived growth factor receptor; STAT: signal transducer and activator of transcription; TKI: tyrosine kinase inhibitors; and VEGFR: vascular endothelial growth factor receptor.