Table 1.
Main trials of ICIs for advanced HCC
| Name | Drugs | Setting | Phase (n) |
Results |
|---|---|---|---|---|
|
CheckMate-040 |
Nivolumab From 0.1 to 10 mg/kg Q2W (Dose escalation) 3 mg/kg Q2W (Dose expansion) |
II line after sorafenib failure/intolerance |
I/II dose escalation (48) Dose expansion (214) |
ORR (mRECIST): 15% (dose-escalation group); 20% (dose-expansion group) mOS: 15.1 months FDA-approved 2017 II line in CPS-A or -B after sorafenib |
|
CheckMate-459 |
Nivolumab 240 mg Q2W vs. sorafenib 400 mg bid | I line |
III open-label Nivolumab (371) Sorafenib (372) |
mOS: 16.8 vs. 14.7 months (p: 0.07) ORR: 15% |
|
CheckMate-040 Cohort 4 |
Nivolumab 1 mg/kg (arm A) or 3 mg/kg (arm B) Q3W Plus ipilimumab 3 mg/kg (arm A) or 1 mg/kg (arm B), Q3W × 4 followed by nivolumab 240 mg Q2W or nivolumab 3 mg/kg Q2W plus ipilimumab 1 mg/kg Q6W (arm C) |
II line after sorafenib failure/intolerance |
I/II Arm A (50) Arm B (49) Arm C (49) |
ORR (mRECIST): 31% (Arm A): 27% (Arm B): 29% (Arm C): mOS: 22.8 months (arm A); 12.5 months (arm B); 12.7 months (arm C) FDA-approved 2020 II line in CPS-A after sorafenib |
|
CheckMate-9DW |
Nivolumab 1 mg/kg Q3W plus ipilimumab 3 mg/kg Q3W × 4 followed by nivolumab 240 mg Q2W vs. lenvatinib 12 or 8 mg qd or sorafenib 400 mg bid |
I line | III open-label (650) 1:1 |
Pending Primary endpoint: OS Completion date: September 2023 |
| NCT04393220 | Nivolumab 480 mg Q4W plus bevacizumab 15 mg/kg Q3W | I line | II open-label (60) |
Pending Primary endpoints: PFS and OS Completion date: October 2021 |
|
Keynote-224 |
Pembrolizumab 200 mg Q3W | II line after sorafenib failure/intolerance | II (104) |
ORR (mRECIST): 17%; mPFS: 4.9 months; mOS: 12.9 months FDA-approved 2018 II line in CPS-A after sorafenib |
|
Keynote-240 |
Pembrolizumab 200 mg Q3W vs. placebo | II line after sorafenib failure/intolerance |
III double-blind Nivolumab (278) Placebo (135) |
mOS: 13.9 vs. 10.6 months (p: 0.02); mPFS: 3 vs. 2.8 months (p: 0.002) |
|
Keynote-524 |
Pembrolizumab Q3W plus lenvatinib 12 or 8 mg qd | I line | Ib (104) | ORR (mRECIST): 46%; mPFS: 9.3 months; mOS: 22 months |
|
LEAP-002 |
Pembrolizumab Q3W plus lenvatinib 12 or 8 mg qd vs. lenvatinib 12 or 8 mg qd plus placebo Q3W | I line |
III double-blind (750) 1:1 |
Pending Primary endpoints: OS and PFS Completion date: May 2023 |
| NCT02715531 | Atezolizumab 1200 mg Q3W plus bevacizumab 15 mg/kg Q3W or atezolizumab 1200 mg Q3W | I line |
Ib Atezo + Beva (60) Atezo (59) |
mPFS: 5.6 vs. 3.4 months; ORR (mRECIST): 27% vs. 17% mOS not reached |
|
IMbrave-150 |
Atezolizumab 1200 mg Q3W plus bevacizumab 15 mg/kg Q3W vs. sorafenib 400 mg bid | I line |
III open-label Atezo + Beva (336) sorafenib (165) 2:1 |
mPFS: 6.8 vs. 4.3 months; ORR: 27.3% vs. 11.9%; OS rate 6 and 12 months: 84.8% and 67.2% vs. 72.2% and 54.6% FDA-approved 2020 I line CPS-A |
|
COSMIC-312 |
Atezolizumab 1200 mg Q3W plus cabozantinib 40 mg qd vs. cabozantinib 60 mg qd vs. sorafenib 400 mg bid | I line |
III open-label (740) 2:1:1 |
Pending Primary endpoints: OS and PFS Completion date: December 2021 |
| NCT01693562 | Durvalumab 10 mg/kg Q2W | II line after sorafenib failure/intolerance | I/II (40) |
ORR: 10.3%; mOS: 13.2 months |
| NCT02519348 | Tremelimumab 300 mg plus durvalumab 1500 mg 1 dose followed by durvalumab Q4W or tremelimumab 75 mg Q4W plus durvalumab 1500 mg Q4W × 4 doses followed by durvalumab Q4W or durvalumab 1500 mg Q4W or tremelimumab 750 mg Q4W | II line after sorafenib failure/intolerance |
II T 300 + D (75) T 75 + D (84) D (104) T (69) |
mOS: 18.7; 11.3; 11.7; 17.1 months; ORR: 22.7%; 11.3%; 11.7%; 17.1% |
|
HIMALAYA |
Durvalumab 1500 mg Q4W or tremelimumab 300 mg plus durvalumab 1500 mg 1 dose followed by durvalumab Q4W or tremelimumab 75 mg Q4W plus durvalumab 1500 mg Q4W × 4 doses followed by durvalumab Q4W or sorafenib 400 mg bid |
III open-label (1324) 1:1:1:1 |
Pending Primary endpoint: OS Completion date: May 2021 |
|
| NCT02572687 | Durvalumab 750 mg Q2W plus ramucirumab 8 mg/kg Q2W | II line after sorafenib failure/intolerance | Ia/b (28) |
mPFS: 4.4 months mOS: 10.7 months |
|
VEGF Liver 100 |
Avelumab 10 mg/kg Q2W plus axitinib 5 mg orally BID | I line | Ib (22) |
ORR (mRECIST): 31.8% mPFS (mRECIST) 3.8 months |
| NCT02989922 | Camrelizumab 3 mg/kg Q2W or Q3W | II line after previous treatment failure/intolerance |
II Q3W (108) Q2W (109) |
ORR: 14.7% OS rate at 6 months 74.7% |
| NCT03463876 | Camrelizumab 200 mg Q2W plus apatinib 125–500 mg qd | II line after previous treatment failure/intolerance |
Ia/b Dose escalation (15) Dose expansion (28) |
ORR (RECIST): 30%; mPFS: 5.8 months; mOS: NR |
| NCT02407990 | Tislelizumab 5 mg/kg Q3W | After at least 1 previous line (median: 2 previous therapies) | Ia/b (50) | ORR (RECIST) 12.2% |
|
RATIONALE 301 |
Tislelizumab 200 mg Q3W vs. sorafenib 400 mg bid | I line |
III open-label (674) |
Pending Primary endpoint: OS Completion date: May 2022 |
|
ORIENT-32 |
Sintilimab 200 mg Q3W plus bevacizumab biosimilar 15 mg/kg Q3W vs. sorafenib 400 mg bid | I line (94%: HBV; 4.2%: CPS-B) |
III open-label Sint + Beva (380) Sorafenib (191) 2:1 |
mOS: NR vs. 10.4 months; 43.1% reduced risk of death with Sint + Beva; mPFS (RECIST): 4.6 vs. 2.8 months ORR (RECIST): 20.5% vs. 4.1% |
| NCT04368078 | Toripalimab 240 mg Q3W plus lenvatinib 12 or 8 mg qd | II line after I line progression with the exception of lenvatinib | II (76) |
Pending Primary endpoint: ORR Completion date: April 2023 |