Targets of immunotherapy for hepatocellular carcinoma: An update

Table 2 Ongoing clinical trials for immune checkpoint inhibitor therapy

Identifier	Type of study	Study design	Status/outcome
NCT02576509 (CheckMate-459)	Global phase III randomized control trial	Comparing nivolumab with sorafenib as first treatment in advanced HCC	Recruitment closed; Results awaited
NCT01658878	Phase I/II dose-escalation, open-label, non-comparative study	Phase 1 to establish the safety of nivolumab at different dose; Phase 2 to compare the efficacy of nivolumab and sorafenib; To study the safety and efficacy of the combination of nivolumab plus ipilimumab and nivolumab plus cabozantinib	Active, not recruiting
NCT03298451	Randomized phase III HIMALAYA trial	To compare the combination of tremelimumab (CTLA-4 inhibitor) and durvalumab (PD-L1 inhibitor) vs sorafenib	Recruiting patients
NCT03680508	Phase II trial	To test efficacy of TSR-022 (cobolimab, TIM-3 binding antibody) and TSR-042 (dostarlimab, PD-1 binding antibody) on advanced HCC	Recruiting patients
NCT02947165	Phase I/Ib study	Anti-TGF-β monoclonal antibody NIS793 and PD-1 inhibitor spartalizumab in breast, lung, colorectal, pancreatic, renal, and HCC	Active, not recruiting
NCT03412773	Phase III randomized, open-label, multicenter, global study	To compare the efficacy and safety of tislelizumab vs sorafenib in unresectable HCC	Active, not recruiting
NCT03434379 (IMbrave150)[51]	Phase III study	To evaluate the efficacy and safety of atezolizumab in combination with bevacizumab compared with sorafenib in locally advanced or metastatic HCC; To determine overall survival	Atezo + Bevac showed improved survival at 18 mo (52%) with clinically meaningful treatment benefit and safety. The trial confirmed atezo + bevac as a standard of care for previously untreated, unresectable HCC
NCT02702401 (MK-3475-240/KEYNOTE-240)	Phase III study	Pembrolizumab (MK-3475) in advanced HCC treated systemically as a second line therapy; To determine overall survival and progression free survival	Active, not recruiting
NCT03062358 (MK-3475-394/KEYNOTE-394)	Phase III study	To determine the efficacy and safety of pembrolizumab or placebo with best supportive care previously systemically treated HCC	Active, not recruiting
NCT03383458 (CheckMate 9DX)	Phase III study	To investigate if nivolumab will improve recurrence-free survival compared to placebo in HCC undergone complete resection	Active, not recruiting

CTLA-4: Cytotoxic T lymphocyte protein 4; PD-1: Programmed cell death protein 1; HCC: Hepatocellular carcinoma; TGF: Transforming growth factor; TIM3: T cell immunoglobulin and mucin domain-containing protein 3.