Table 4

Landmark trials leading to FDA approvals for immunotherapy for HCC

Trial (NCT#)PhaseAgent(s) evaluatedStudy populationPatientsOutcomes
CheckMate 040
(NCT01658878)
I/IINivolumab*†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.262ORR 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)IPembrolizumab*Patients with disease progression on or after sorafenib or intolerant to sorafenib, and measurable CP A disease.104ORR 17%
(95% CI 11% to 26%)
CheckMate 040
(NCT01658878)
I/IINivolumab+ipilimumab*Patients with histologically confirmed advanced HCC with or without HCV or HBV infection. Previous sorafenib treatment was allowed.148ORR 33%
(95% CI 20% to 48%)
IMbrave150‡IIIAtezolizumab+
bevacizumab vs sorafenib
Patients with unresectable HCC who had received no prior systemic therapy and had well-compensated liver disease.501OS HR 0.58 (95% CI 0.42 to 0.79; p<0.001)


ORR 27.3% vs 11.9% (p<0.001)
  • *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  • †Indication voluntarily withdrawn July 2021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.