Table 4.

Landmark trials leading to FDA approvals for immunotherapy for HCC

Trial (NCT#)	Phase	Agent(s) evaluated	Study population	Patients	Outcomes
CheckMate 040 (NCT01658878)	I/II	Nivolumab*†	Patients with histologically confirmed advanced HCC with or without HCV or HBV infection. Previous sorafenib treatment was allowed. CP A or B7 disease for dose escalation; CP A disease for dose expansion.	262	ORR 20% (95% CI 15% to 26%) in dose-expansion phase ORR 14.3% (95% CI 6% to 28%) in population with progressive disease on/intolerance to sorafenib
KEYNOTE-224 (NCT02702414)	I	Pembrolizumab*	Patients with disease progression on or after sorafenib or intolerant to sorafenib, and measurable CP A disease.	104	ORR 17% (95% CI 11% to 26%)
CheckMate 040 (NCT01658878)	I/II	Nivolumab+ipilimumab*	Patients with histologically confirmed advanced HCC with or without HCV or HBV infection. Previous sorafenib treatment was allowed.	148	ORR 33% (95% CI 20% to 48%)
IMbrave150‡	III	Atezolizumab+ bevacizumab vs sorafenib	Patients with unresectable HCC who had received no prior systemic therapy and had well-compensated liver disease.	501	OS HR 0.58 (95% CI 0.42 to 0.79; p<0.001) ORR 27.3% vs 11.9% (p<0.001)
HIMALAYA (NCT03298451)	III	Tremelimumab + durvalumab vs sorafenib	Patients with unresectable HCC and no previous systemic treatment	782	OS HR 0.78 (96.02% CI 0.65 to 0.93; p = 0.0035) ORR 20.1% vs 5.1%

*Accelerated approval contingent on confirmatory trials

†Indication voluntarily withdrawn July 2021

‡Updated data with 12 additional months of follow-up found ORR of 29.8% (95% CI 24.8% to 35.0%) for atezolizumab+bevacizumab versus 11.3% (95% CI 6.9% to 17.3%) for sorafenib66

CI, confidence interval; CP, Child-Pugh; FDA, US Food and Drug Administration; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HR, hazard ratio; ORR, overall response rate; OS, overall survival.