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†Indication voluntarily withdrawn July 2021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.