Immunotherapy in hepatocellular carcinoma: Combination strategies

Table 4 Summary of active clinical trials evaluating combination therapy of checkpoint inhibitors plus vascular endothelial growth factor/factor receptor inhibitors

Therapy	Comparator	Therapy indication	Phase	Estimated study duration	Estimated patient enrollment	Primary endpoints	Trial identifier
Atezolizumab plus bevacizumab	None	First-line	II	January 1, 2020-June 30, 2022	48	Best overall response rate	NCT04180072
Atezolizumab plus bevacizumab	Sorafenib	First-line	III	March 15, 2018-June 29, 2022	480	OS, PFS	NCT03434379 (IMbrave 150)
Atezolizumab plus bevacizumab	Active surveillance	Adjuvant	III	December 31, 2019-July 12, 2027	662	RFS	NCT04102098 (IMbrave 150)
Durvalumab plus bevacizumab	Durvalumab alone vs tremelimumab alone vs durvalumab plus tremelimumab (regimen 1 vs regimen 2) vs durvalumab plus bevacizumab	First-line	II	October 19, 2015-January 6, 2021	433	Number patients experiencing adverse events and dose-limiting toxicities	NCT02519348
Durvalumab plus bevacizumab	Durvalumab plus placebo vs placebo alone	Adjuvant	III	April 29, 2019-June 16, 2023	888	RFS	NCT03847428 (EMERALD-2)
Camrelizumab plus apatinib	None	Second-line	II	June 1, 2019 – October 1, 2020	40	ORR	NCT04014101
Camrelizumab plus apatinib	Hepatic arterial infusion of chemotherapy	Adjuvant	II	February 15, 2019-February 28, 2023	200	RFS	NCT03839550
Camrelizumab plus apatinib and hepatic arterial infusion of FOLFOX chemotherapy regimen	None	Not specified	II	April 13, 2020-December 31, 2025	84	ORR	NCT04191889
Camrelizumab plus apatinib	Sorafenib	First-line	III	June 10, 2019-June 2022	510	OS, PFS	NCT03764293

OS: Overall survival; PFS: Progression-free survival; RFS: Recurrence-free survival; ORR: Overall response rate.