Table 1 Clinical trials conducted with ICIs (monotherapy and combination therapy) in HCC
Target | Drug | epitope | Intervention | Phase | Status | Trial ID | Refs. |
|---|---|---|---|---|---|---|---|
Monotherapy | |||||||
 PD-1 | Nivolumab | PD-1N-loop | – | III | Active, not recruiting | NCT03383458 | [104] |
 PD-1 | Pembrolizumab | PD-1 CD loop | – | II | Active, not recruiting | NCT02702414 | [105] |
 PD-1 | Pembrolizumab | PD-1 CD loop | – | III | Completed | NCT02702401 | [106] |
 PD-1 | Pembrolizumab | PD-1 CD loop | – | III | Active, not recruiting | NCT03062358 | [107] |
 PD-1 | Tislelizumab | PD-1 CC’ loop | – | I | Completed | NCT02407990 | [108] |
 PD-L1 | Durvalumab | PD-1 C, F, G, CC’ loop and N-terminal | – | II | Completed | NCT01693562 | [109] |
 PD-L1 | Avelumab | C, C′, F, G and CC′ loop of PD-L1 | – | II | Completed | NCT03389126 | [110] |
Combination therapy | |||||||
 PD-L1 | Atezolizumab | PD-L1 CC′FG antiparallel β-sheet and the BC, CC′, C′C″, and FG loops | Bevacizumab | I | Completed | NCT02715531 | [111] |
 PD-L1 | Atezolizumab | PD-L1 CC′FG antiparallel β-sheet and the BC, CC′, C′C″, and FG loops | Cabozantinib | I, II | Recruiting | NCT03170960 | [112] |
 PD-1 | Nivolumab | PD-1N-loop | Cyclophosphamide IRX-2 | I | Recruiting | NCT03655002 | [113] |
 PD-1 | Nivolumab | PD-1N-loop | Fluorouracil Recombinant Interferon Alpha 2b-like Protein | I, II | Recruiting | NCT04380545 | [114] |
 PD-1 | Sintilimab | FG loop on PD-1 | Lenvatinib TACE-HAIC | II | Recruiting | NCT04814043 | [115] |
 PD-1, PD-L1 | Pembrolizumab Nivolumab Atezolizumab Avelumab Durvalumab | PD-1 CD loop PD-1N-loop, PD-1 C, F, G, CC’ loop and N-terminal, PD-L1 CC′FG antiparallel β-sheet and the BC, CC′, C′C″, and FG loops | N-803 | II | Active, not recruiting | NCT03228667 | [116] |
 PD-1 | Nivolumab | PD-1N-loop | Radiofrequency Ablation | IV | Completed | NCT04707547 | [117] |
 PD-1 | Nivolumab | PD-1N-loop | Regorafenib | II | Recruiting | NCT04310709 | [118] |
 PD-1, CTLA-4 | Durvalumab Tremelimumab | PD-1 C, F, G, CC’ loop and N-terminal | SBRT | II | Recruiting | NCT04988945 | [119] |
 CTLA-4 | Tremelimumab | CDR loops | Sorafenib | II | Active, not recruiting | NCT01008358 | [85] |
 PD-1 | Nivolumab | PD-1N-loop | Sorafenib | II | Active, not recruiting | NCT01658878 | [120] |
 PD-1 | Nivolumab | PD-1N-loop | Sorafenib | III | Active, not recruiting | NCT02576509 | [121] |
 PD-1 | Tislelizumab | PD-1 CCʹ loop | Sorafenib | III | Active, not recruiting | NCT03412773 | [122] |
 PD-1 | Anti-PD-1 | Not mentioned | TACE-HAIC | II | Recruiting | NCT04814030 | [123] |