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

Table 3 Ongoing clinical trials of tyrosine kinase inhibitors as second-line systemic treatments for hepatocellular carcinoma following progression to immune checkpoint inhibitors

Study	Status	Description	Phase	Study design	Treatment arms	Number of patients	Population	Primary endpoint
NCT06138769	Active, not recruiting	Lenvatinib after progression on atezolizumab-bevacizumab in hepatocellular carcinoma	Phase 2	Single-arm	Lenvatinib	50	Progressed on atezo-bev; Child-Pugh A; PS 0-1	PFS
NCT04767906 (capture)	Completed	Cabozantinib treatment in a phase II study for patients with hepatocellular carcinoma refractory to PD-1 inhibitors	Phase 2	Single-arm	Cabozantinib	40	Progressed on PD-1 or PD-L1 inhibitor; Child-Pugh A; PS 0-1; BCLC B/C	ToT
NCT04511455	Completed	Cabozantinib for patients with hepatocellular carcinoma refractory to first line treatment	Phase 2	Single-arm	Cabozantinib	22	Progressed on lenvatinib or lenvatinib + ICIs; Child-Pugh A-B7; PS 0-1	ToT
NCT0653573 (Child-Pugh AB)	Not yet recruiting	A phase 2, single arm study of cabozantinib in patients with hepatocellular carcinoma who have received prior atezolizumab and bevacizumab	Phase 2	Single-arm	Cabozantinib	40	Progressed on atezo-bev; Child-Pugh A-B7; PS 0-1	DCR
NCT06446154	Recruiting	Fruquintinib after ICIs treatment in unresectable hepatocellular carcinoma	Phase 2	Single-arm	Fruquintinib	36	Progressed on ICIs; Child-Pugh A-B7; PS 0-1	ORR
NCT05134532	Unknown status	Regorafenib after progression on atezolizumab plus bevacizumab in advanced hepatocellular carcinoma	Phase 2	Single-arm	Regorafenib	40	Progressed on atezo-bev; Child-Pugh A; PS 0-1	PFS
NCT04435977	Unknown status	Efficacy and safety of cabozantinib in patients with hepatocellular carcinoma	Phase 2	Single-arm	Cabozantinib	46	Progressed on ICIs; Child-Pugh A; PS 0-1	PFS

NCT: National clinical trial; PD-1: Programmed death-1; ICIs: Immune checkpoint inhibitors; atezo-bev: Atezolizumab-bevacizumab; PS: Performance status; PD-L1: Programmed cell death ligand 1; BCLC: Barcelona Clinic Liver Cancer; PFS: Progression-free survival; DCR: Disease control rates; ToT: Time-on-treatment; ORR: Objective response rates.