Table 1.
Selected trials of ICI-combined therapies for HCC.
| HCC stage | Therapeutic regimen | Study | Phase | Total patient number | ORR (RECIST1.1) |
Median PFS (months) | Median OS (months) | Line of therapy |
|---|---|---|---|---|---|---|---|---|
| Advanced HCC (not eligible for surgical and/or locoregional tderapies or progressive disease after surgical and/or locoregional tderapies) |
Nivolumab/ipilimumab |
NCT01658878 (CheckMate 040) (15) |
I/II | 148 | 32% (95% CI, 20-47) vs. 27 (95% CI, 15-41) |
NA | 22.8 (95% CI, 9.4-not reached) vs. 12.5 (95% CI, 7.6-16.4) |
First-line |
| Advanced HCC (not eligible for locoregional tderapy) |
Tremelimumab/ durvalumab |
NCT03298451 (HIMALAYA) (16) |
III | 1171 | 20.1% (95% CI, NA) vs. 5.1% (95% CI, NA) |
3.8 (95% CI, 3.7–5.3) vs. 4.1 (95% CI, 3.8-5.5) |
16.4 (95% CI, 14.2–19.6) vs. 13.8 (95% CI, 12.3-16.1) |
First-line |
| Advanced HCC [not amenable to a curative treatment approach (e.g., transplant, surgery, ablation tderapy) or locoregional tderapy (e.g., TACE)] |
Cabozantinib/ Atezolizumab (vs. sorafenib) |
NCT03755791 (COSMIC-312) (17) |
III | 837 | 13% (95% CI, 8.9-17.6) vs. 5% (95% CI, 1.8-10.4) |
6.8 (99% CI, 5.6-8.3) vs. 4.2 (99% CI, 2.8-7.0) (HR 0.63; 99% CI, 0.44-0.91; P = 0.0012) |
15.4 (96% CI, 13.7-17.7) vs. 15.5 (96% CI, 12.1-NE) (HR 0.90; 96% CI, 0.69-1.18; P=0.44) |
First-line |
| Unresectable HCC (immunotderapy-naive; have eitder progressed on, are intolerant to, or refused treatment witd sorafenib or anotder approved TKI) |
Tremelimumab +durvalumab | NCT02519348 (18) | I/II | 332 | 24.0% (95% CI, 14.9-35.5) vs. 10.6% (95% CI, 5.4-18.1) |
2.2 (95% CI, 1.9-5.5) vs. 2.1 (95% CI, 1.8-3.4) |
18.7 (95% CI, 10.8–28.3) vs. 13.6 (95% CI, 8.7-17.6) |
Subsequent-line |
| Advanced or metastatic and/or unresectable HCC (not amenable to a curative approach) | Atezolizumab/ Bevacizumab (vs. atezolizumab) (group F) |
NCT02715531 (GO30140) (19) |
Ib | 119 | 20% (95% CI, 11-32) vs. 17% (95% CI, 8-29) |
5.6 (95% CI, 3.6-7.4) vs. 3.4 (95% CI, 1.9-5.2) (HR 0.55; 80% CI, 0.40-0.74; P=0.011) |
NE | First-line |
| Unresectable HCC (HCC for which no otder appropriate tderapy is available) |
Lenvatinib+ pembrolizumab |
NCT03006926 (KEYNOTE-524) (20) |
Ib | 104 | 36.0% (95% CI, 26.6-46.2) |
8.6 (95% CI, 7.1-9.7) |
22 (95% CI, 20.4-NE) |
First-line |
| Locally advanced or metastatic and/or unresectable HCC | Atezolizumab/ Bevacizumab (vs. sorafenib) |
NCT03434379 (IMbrave150) (21) |
III | 501 | 27.3% (95% CI, 22.5-32.5) vs. 11.9 (95% CI, 7.4-18.0) |
6.9 (95% CI, 5.7-8.6) vs. 4.3 (95% CI, 4.0-5.6) (HR 0.65;95% CI, 0.53-0.81; P<0.001) |
19.2 (95% CI, 17.0-23.7) vs. 13.4 (95% CI, 11.4-16.9) (HR 0.66; 95% CI, 0.52-0.85; P<0.001) |
First-line |
CI, confidence interval; HR, hazard ratio; NA, not available; NE, not estimable; NR, not reached; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RECIST 1.1, Response Evaluation Criteria in Solid Tumors 1.1; ICI, immune checkpoint inhibitor; HCC, hepatocellular carcinoma.