Immunotherapy in hepatocellular carcinoma: Combination strategies

Table 2 Reported results of successful clinical trials evaluating immunotherapy in hepatocellular carcinoma patients

Therapy	Comparator	Therapy indication	Phase	Approximate data collection period	Patients enrolled	Primary endpoints	Trial identifier
Nivolumab	None	Not specified	I/II	November 26, 2012-August 8, 2016	214 (dose-escalation), 48 (dose-expansion)	ORR (dose-escalation phase - 15%), (dose-expansion phase – 20%)	NCT01658878 (CheckMate 040)
Pembrolizumab	None	Second-line	II	June 22, 2016- February 20, 2017	104	ORR – 18.3%, median OS 13.2 mo	NCT02702414 (KEYNOTE-224)
Camrelizumab	Camrelizumab (regimen 1) vs camrelizumab (regimen 2)	Second-line	II	November 15, 2016– November 16, 2017	220	ORR 13.8%, median OS not reached	NCT02989922
Durvalumab	None	Not specified	I/II	August 29, 2012-October 24, 2016	40	ORR – 10.3%, median OS 13.2 mo	NCT01693562
Tremelimumab	None	Not specified	II	December 2008-May 2012	21	ORR - 17.6%, DCR 76.4%	NCT01008358
Pembrolizumab	Placebo	Second-line	III	May 31, 2016-November 23, 2017	413	Median OS 13.9 vs 10.6 months – HR: 0.781; 95%CI: 0.611 to 0.998; P = 0.0238, PFS 3.0 vs 2.8 months – HR: 0.718; 95%CI, 0.570 to 0.904; P = 0.0022 (pembrolizumab vs placebo)	NCT02702401
Nivolumab plus ipilimumab	Nivolumab plus ipilimumab (regimen 1 vs regimen 2 vs regimen 3)	Second-line	I/II	Minimum follow-up-28 months at time of data cutoff	148	ORR – (32 - Arm A, 31- Arm B, 31 - Arm C), median DOR (17.5 - Arm A, 22.2 - Arm B, 16.6 - Arm C )	NCT01658878 (CheckMate 040)
Durvalumab plus tremelimumab	None	Second-line	I/II	October 19, 2015-January 10, 2017	40	ORR – 15%	NCT02519348
Atezolizumab plus bevacizumab	Sorafenib	First-line	III	March 15, 2018-November 2019	501	OS HR: 0.58 (95%CI: 0.42- 0.79; P = 0.0006), PFS 6.8 vs 4.3 mo, P < 0.0001 (atezolizumab plus bevacizumab vs sorafenib)	NCT03434379(IMbrave 150)

ORR: Overall response rate; OS: Overall survival; DCR: Disease control rate; PFS: Progression-free survival; DOR: Duration of response; OS HR: Overall survival hazard rate.