TABLE 5.

Published clinical trials involving GPC3, ALK-1, and PD-1 in HCC immunotherapy.

Drug	Combination	Route, dose	Enrollment	Efficacy	Adverse effect	Phase	Ref
GPC3 derived peptide vaccine	None	Intracutaneously, on days 1, 15 and 29, at doses 0.3, 1.0, 3.0, 10, 30 mg/body surface area.	Non-randomized, open label	24/33 lymph node regression, 2 liver tumors disappeared.	Grade III hematologic adverse events (impaired liver function) in 4 patients	I	Sawada et al., 2012
GC33	75% patients received sorafenib	Dose escalation, 2.5–20 mg/kg, weekly i.v.	Multicenter, open label, single arm	AFP levels decreased or stabilized	Grade III, NK cell numbers in plasma decreased.	I	Zhu et al., 2013
Anti-ALK-1 McAb PF-03446962	Antiangiogenic or sorafenib therapy	1 h iv on days 1 and 29 and every 2 weeks thereafter, RP2D of 7 mg/kg.	Single-arm	Disease control rate at 12 weeks was 29%.	Grade III Thrombocytopenia in 33%, grade IV abdominal pain in 1 patient.	I	Simonelli et al., 2016
SHR-1210, an anti-PD-1 McAb	Apatinib, a VEGFR2 Inhibitor	Oral apatinib once-daily combined with SHR-1210 administered intravenously every 2 weeks.	Single center, open label.	Objective response rate is 30.8%, partial response is 50%.	Grade III Lipases rise (6.7%), preumonitis (20%) Hypertension (15.2%), increased AAT 15.2%.	Ia and Ib	Xu et al., 2019