Post-immunotherapy second-line strategies for hepatocellular carcinoma: State of the art and ongoing trials

Table 1 Ongoing clinical trials of immune checkpoint inhibitors-based second-line systemic treatments for hepatocellular carcinoma

Study	Status	Description	Phase	Study design	Treatment arms	Number of patients	Population	Primary endpoint
NCT04770896 (imbrave 251)	Active, not recruiting	A study of atezolizumab with lenvatinib or sorafenib vs lenvatinib or sorafenib alone in hepatocellular carcinoma previously treated with atezolizumab and bevacizumab	Phase 3	RCT	Atezolizumab + lenvatinib or sorafenib; lenvatinib or Sorafenib	554	Progressed on atezo-bev; Child-Pugh A; PS 0-1	OS
NCT05168163	Recruiting	Atezolizumab in combination with a multi-kinase inhibitor for the treatment of unresectable, locally advanced, or metastatic liver cancer	Phase 2	RCT	Atezolizumab + cabozantinib or Lenvatinib; cabozantinib or lenvatinib	122	Progressed on atezo-bev; Child-Pugh A, PS 0-1	OS, PFS
NCT05822752	Active, not recruiting	Study to evaluate adverse events, and change in disease activity, when IV infused with livmoniplimab in combination with IV infused budigalimab in adult participants with HCC	Phase 2	RCT	Lenvatinib or sorafenib; livmoniplimab dose A + budigalimab; livmoniplimab dose B + budigalimab	130	Progressed on ICI regimens; Child-Pugh A; PS 0-1	BOR
NCT04696055	Completed	An open-label study of regorafenib in combination with pembrolizumab in patients with advanced or metastatic HCC After PD1/PD-L1 immune checkpoint inhibitors	Phase 2	Single-arm	Pembrolizumab + regorafenib	95	Progressed on ICIs regimens; Child-Pugh A, PS 0-1	ORR
NCT05101629	Active, not recruiting	Pembrolizumab and lenvatinib in patients with advanced HCC who are refractory to atezolizumab and bevacizumab/io-based therapy	Phase 2	Single-arm	Pembrolizumab + lenvatinib	32	Progressed on atezo-bev; Child-Pugh A; PS 0-1	ORR
NCT05199285	Recruiting	A phase II study of nivolumab + ipilimumab in advanced HCC patients who have progressed on first line atezolizumab + bevacizumab	Phase 2	Single-arm	Nivolumab + ipilimumab	40	Progressed on atezo-bev; Child-Pugh A; PS 0-1	ORR
NCT05257590	Recruiting	CVM-1118 in combination with nivolumab for unresectable advanced hepatocellular carcinoma	Phase 2	Single-arm	Nivolumab + CVM-1118	31	Progressed on atezo-bev or TKIs; child Pugh A, PS 0-1	ORR
NCT05178043	Active, not recruiting	GT90001 plus nivolumab in patients with advanced hepatocellular carcinoma	Phase 2	Single-arm	Nivolumab + GT90001	5	Progressed on ICI or ICI + TKI; Child-Pugh A; PS 0-1	ORR

NCT: National clinical trial; HCC: Hepatocellular carcinoma; IV: Intravenously; PD-1: Programmed death-1; PD-L1: Programmed cell death ligand 1; RCT: Randomized clinical trial; ICIs: Immune checkpoint inhibitors; PS: Performance status; TKI: Tyrosine kinase inhibitor; OS: Overall survival; PFS: Progression-free survival; BOR: Best overall response; ORR: Objective response rate; atezo-bev: Atezolizumab-bevacizumab.