Immunotherapy in hepatocellular carcinoma: Combination strategies

Table 5 Summary of active clinical trials evaluating combination therapy of checkpoint inhibitors plus tyrosine kinase inhibitors

Therapy	Comparator	Therapy indication	Phase	Estimated study duration	Estimated patient enrollment	Primary endpoints	Trial identifier
Nivolumab plus sorafenib	Nivolumab plus sorafenib (regimen 1 vs regimen 2)	First-line	II	April 16, 2018-May 31, 2020	40	MTD, ORR	NCT03439891
Pembrolizumab plus sorafenib	None	First-line	Ib/II	September 13, 2017-September 13, 2021	27	ORR	NCT03211416
Nivolumab plus lenvatinib	None	First-line	II	June 12, 2019-October 2021	50	ORR, safety/tolerability	NCT03841201
Pembrolizumab plus lenvatinib	Placebo plus lenvatinib	First-line	III	December 31, 2018-May 13, 2022	750	PFS, OS	NCT03713593 (LEAP-002)
Nivolumab plus cabozantinib	Nivolumab plus Ipilimumab plus cabozantinib	Not Specified	I/II	September 26, 2012-April 29, 2022	1097	Safety and tolerability	NCT01658878 (CheckMate 040)
Nivolumab plus Ipilimumab plus cabozantinib	Nivolumab plus cabozantinib	Not Specified	I/II	September 26, 2012-April 29, 2022	1097	Safety and tolerability	NCT01658878 (CheckMate 040)
Atezolizumab plus cabozantinib	Sorafenib vs cabozantinib	First-line	III	December 10, 2018-December 1, 2021	740	Duration of PFS, duration of OS	NCT03755791 (COSMIC-312)
Nivolumab plus regorafenib	None	Second-line	I/II	March 16 2020-December 2022	60	Rate of adverse events, rate of death	NCT04170556 (GOING)
Nivolumab plus regorafenib	None	First-line	II	May 30, 2020-May 30, 2023	42	Response rate	NCT04310709 (RENOBATE)

MTD: Maximum tolerated dose; ORR: Overall response rate; PFS: Progression-free survival; OS: Overall survival.