MET inhibitors for treatment of advanced hepatocellular carcinoma: A review

Table 1 Overview of important clinical trials

First author, Journal (Year)	Study design	Enrollment period	Drugs	Patients	No. Pts
Santoro, BJC (2013)	Phase I, open-label, single-arm study (full-text), NCT00802555	2009.3- 2010.11 completed	Tivantinib	Advanced HCC, Child-Pugh A cirrhosis, previously treated with sorafenib or other therapy	21
Santoro, Lancet Oncol (2013)	Phase II double-blind, placebo-controlled, RCT (full-text), NCT00988741	2009.10.8- 2011.8.25 completed	Tivantinib vs placebo	Advanced HCC with or without MET-high tumors, who had progressed on or were unable to tolerate first-line systemic therapy	107
Verslype/Cohn, JCO (2012, May/Feb)	Phase II randomized discontinuation trial (abstract), NCT00940225	Completed	PR: Continued open-label cabozantinib; SD: Cabozantinib vs placebo; PD: Discontinued	Advanced HCC, ≤ 1 prior systemic regimen, Child-Pugh A	41
Novartis Pharmaceuticals	Phase II, open label, single-arm study (registration), NCT01737827	Ongoing	INC280	Advanced HCC which could not be suitable for treatment with locoregional therapies or has progressed following locoregional therapy, c-MET pathway dysregulation	56
Novartis Pharmaceuticals	Phase II, double-blind, placebo-controlled RCT (registration), NCT01964235	Suspended	INC280 vs placebo	Adult patients with advanced HCC after progression or intolerance to sorafenib treatment, c-MET pathway dysregulation	69
Merck KGaA	Phase Ib/II, single-arm, trial (registration), NCT02115373	Ongoing	MSC2156119J	Advanced HCC, MET+, Child-Pugh A, who have failed sorafenib treatment	48
Qin, JCO (2014)	Phase Ib/II RCT (abstract), NCT01988493	Ongoing	Phase II: MSC2156119J vs sorafenib	Asian patients, MET-positive, advanced HCC, Child-Pugh A	158
O'Neil, JCO (2013)	Phase Ib/II, open-label, study (abstract), NCT01271504	Ongoing	Phase Ib: Golvatinib plus sorafenib; Phase II: Golvatinib plus sorafenib vs sorafenib alone	Advanced HCC	13
Yau, JCO (2012)	Phase I/II trial (abstract), NCT00920192	Ongoing	Foretinib	Advanced HCC	13
Santoro, JCO (2013)	Phase III, double-blind, RCT (abstract), NCT01755767	Ongoing	Tivantinib vs placebo	MET diagnostic-high inoperable HCC treated with one prior systemic therapy	303
Abou-Alfa, JCO (2014)	Phase III, double-blind, RCT (abstract), NCT01908426	Ongoing	Cabozantinib vs placebo	Advanced HCC who have received prior sorafenib	760

SD: Stable disease; HCC: Hepatocellular carcinoma; PD: Progressive disease; PR: Partial response; RCT: Randomized controlled trial.