Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy

Table 1 Summary of clinical study data for hepatocellular carcinoma immunotherapy

Study	NCT ID	Study phase	Patient population	Sample size	Intervention measures	Finding	Region
Checkmate 040	NCT01658878	I/II	Advanced HCC with or without chronic viral hepatits	659	Envafolimab/Pembrolizumab	ORR: 15% vs 20%; DCR: 58% vs 64%; median TTP: 3.4 months vs 4.1 months; median DOR: 17 months vs 9.9 months	Asia, Europe, United States
Keynote 224	NCT02702414	II	Advanced HCC	156	Pembrolizumab	ORR: 17%; DCR: 62%; mPFS: 4.9 months; mOS: 12.9%	Asia, Europe, North America
Reflect	NCT01761266	Ⅲ	Unresectable HCC	954	Lenvatinib/Sorafenib	mOS: 13.6 months vs 12.3 months; mPFS: 7.4 months vs 3.7 months; medianTTP: 8.9 months vs 3.7 months; ORR: 24.1% vs 9.2%	Asia, Europe, North America
Keynote 524	NCT03006926	I	HCC	104	Pembrolizumab + Lenvatinib	ORR: 46% vs 36%; DCR: 88% vs 88%; median DOR: 8.6 months vs 12.6 months; mPFS: 9.3 months vs 8.6 months; mOS: 22 months vs 22 months	United States, France, Italy, Japan
Leap002	NCT03713593	III	Advanced HCC	794	Pembrolizumab + Lenvatinib/Lenvatinib	mOS: 21.1 months vs 19.0 months; mPFS: 8.2 months vs 8.0 months; ORR: 26.1% vs 17.5%; DCR: 81.3% vs 78.4%	Asia, Europe, United States
Study117	NCT03418922	Ib	HCC	30	Lenvatinib + Nivolumab	ORR: 37.5% vs 7.7%; DCR: 62.5% vs 69.2%; 12 mPFS: 30.0% vs 49.2%; 12 mOS: 52.1% vs 51.3%	NA
COSMIC-312	NCT03755791	III	Advanced HCC without prior systemic anticancer therapy	837	Cabozantinib + Atezolizumab/Cabozantinib + Sorafenib	mPFS: 6.8 months vs 4.2 months; mOS: 15.4 months vs 15.5 months; ORR: 13% vs 5%; DCR: 82% vs 63%	Asia, Europe, United States
RESCUE	NCT03463876	Ⅱ	Advanced HCC	190	Camrelizumabfor + Apatinib	ORR: 34.3% vs 23.8%; DCR: 77.1% vs 75.8%; median DOR: 14.8 months vs NE; mPFS: 5.7 months vs 5.5 months	NA
Imbrave 150	NCT03434379	III	locally advanced or metastatic HCC	558	Atezolizumab + Bevacizumab/Sorafenib	ORR: 33.2% vs 13.3%; DCR: 72.3% vs 55.1%; median DOR: NE vs 6.3 months	Asia, Europe, United States
ORIENT-32	NCT03794440	II/III	Advanced HCC	571	Sintilimab + Bevacizumab/Sorafenib	mOS: NE vs 10.4 months; mPFS: 6.9 months vs 4.3 months; ORR: 24% vs 8%	China
Study 22	NCT02519348	Ⅱ	Advanced HCC	332	Tremelimumab + Durvalumab/Tremelimumab/Durvalumab	mOS: 18.7 months vs 13.6 months vs 15.1 months vs 11.3 months; DCR: 34% vs 39% vs 34% vs 31%; ORR: 24% vs 10.6% vs 7.2% vs 9.5%; median DOR: NR vs 11.17 months vs 23.95 months vs 13.21 months	Asia, United States, Italy
HIMALAYA	NCT03298451	III	No prior systemic therapy for unresectable HCC	1504	Tremelimumab/Durvalumab	OS: 16.4 months vs 13.8 months; ORR: 20.1% vs 5.1%	Asia, Europe, United States
Checkmate-9DW	NCT04039607	III	No prior systemic therapy for Advanced HCC	732	Nivolumab + Pembrolizumab/Sorafenib/Lenvatinib	NE	Asia, Europe, United States
CHANCE001	NCT04975932	Retrospective study	HCC	556	TACE + PD-L1 inhibitors + Inhibitor molecule targeted drugs/TACE	mPFS: 9.5 months vs 8.0 months; mOS: 19.2 months vs 15.7 months; ORR: 60.1% vs 32.0%	China

HCC: Hepatocellular carcinoma; NA: Not Available; TACE: Transcatheter arterial chemoembolization; MTT: Molecular targeted therapy; PFS: Progressive free survival; ORR: Objective response rate; DCR: Disease control rate; NR: Not reported; TTP: Time to progression; NCT: National clinical trials; OS: overall survival; PD-L1: programmed death ligand-1; DOR: During of response; mPFS: Median PFS; mOS: Median OS; NE: Not estimable.