Immunotherapy in hepatocellular carcinoma: Combination strategies

Table 3 Summary of active clinical trials evaluating checkpoint inhibitor combination therapy

Therapy	Comparator	Therapy indication	Phase	Estimated study duration	Estimated patient enrollment	Primary endpoints	Trial identifier
Nivolumab plus ipilimumab	None	Neoadjuvant	I/II	March 1, 2019-September 1, 2022	32	Delay to surgery, incidence of treatment-related adverse events	NCT03682276 (PRIME-HCC)
Nivolumab plus ipilimumab	Nivolumab vs nivolumab plus ipilimumab (regimen 1) vs nivolumab plus ipilimumab (regimen 2)	Neoadjuvant	II	September 28, 2017-September 30, 2022	45	Incidence of adverse events	NCT03222076
Nivolumab plus ipilimumab	None	Neoadjuvant	II	June 1, 2018-December 31, 2022	40	Percentage of subjects with tumor shrinkage after therapy	NCT03510871
Nivolumab and ipilimumab plus INCAGN01876 (OX-40 Agonist)	Nivolumab plus INCAGN01876 vs ipilimumab plus INCAGN01876	Not specified	I/II	April 13, 2017-October 28, 2021	285	Safety and tolerability, ORR	NCT03126110
Nivolumab plus ipilimumab	Sorafenib or lenvatinib	First-line	III	September 16, 2019 – September 16, 2023	1084	OS	NCT04039607 (CheckMate 9DW)
Durvalumab plus tremelimumab	Durvalumab vs tremelimumab vs durvalumab plus tremelimumab (regimen 1) vs durvalumab plus tremelimumab (regimen 2) vs durvalumab plus bevacizumab	Second-line (first-line for patients receiving durvalumab plus bevacizumab)	II	October 19, 2015-January 6, 2021	433	Number patients experiencing adverse events and dose-limiting toxicities	NCT02519348
Durvalumab plus tremelimumab	Durvalumab vs durvalumab plus tremelimumab (regimen 1) vs durvalumab plus tremelimumab (regimen 2) vs sorafenib	First-line	III	October 11, 2017-October 30, 2020	1310	OS	NCT03298451 (HIMALAYA)

HCC: Hepatocellular carcinoma; ORR: Overall response rate; OS: Overall survival.