Table 4:
Selected ongoing phase I-III trials for advanced HCC
| Agent(s) (Targets) | Primary endpoint | Line of treatment | Phase | Sample size | NCT |
|---|---|---|---|---|---|
| ICI combinations with targeted therapies | |||||
| Pembrolizumab (PD1), lenvatinib (VEGFR1–3, PDGFR, FGFR1–4, RET) | OS, PFS | 1st | III | 750 | NCT03713593 |
| Atezolizumab (PD-L1), cabozantinib (VEGFR1–3, MET, RET) | OS, PFS | 1st | III | 740 | NCT03755791 |
| AK105 (PD1), anlotinib (VEGFR1–3, FGFR1–4, PDGFR, KIT receptor) | OS | 1st | III | 648 | NCT04344158 |
| Camrelizumab (PD1), apatinib (VEGFR2) | OS, PFS | 1st | III | 510 | NCT03764293 |
| Tislelizumab (PD1), lenvatinib (VEGFR1–3, PDGFR, FGFR1–4, RET) | ORR | 1st | II | 66 | NCT04401800 |
| Nivolumab (PD1), sorafenib (VEGFR1–3, PDGFR, RAF kinase, KIT receptor) | ORR, MTD | 1st | II | 12 | NCT03439891 |
| Pembrolizumab (PD1), sorafenib (VEGFR1–3, PDGFR, RAF kinase, KIT receptor) | ORR | 1st | I/II | 27 | NCT03211416 |
| HX008 (PD1), bevacizumab (VEGFA), lenvatinib (VEGFR1–3, PDGFR, FGFR1–4, RET) | ORR | 1st | II | 72 | NCT04741165 |
| CS1001 (PD-L1), fisogatinib (FGFR4) | ORR, DLT | 1st or 2nd | Ib/II | 52 | NCT04194801 |
| Pembrolizumab (PD1), regorafenib (VEGFR1–3, PDGFR, RAF kinase, FGFR1–2) | ORR | 2nd | II | 119 | NCT04696055 |
| Atezolizumab (PD-L1), sorafenib (VEGFR1–3, PDGFR, RAF kinase, KIT receptor), lenvatinib (VEGFR1–3, PDGFR, FGFR1–4, RET) | OS | 2nd | III | 554 | NCT04770896 |
| PDR001 PD1, INC280/campatinib (MET) | ORR, DLT | 2nd | Ib/II | 90 | NCT02795429 |
| Tislelizumab (PD1), sitravatinib (TYRO3, AXL, MERTK, VEGFR2, KIT receptor, MET) | ORR, incidence of AEs/SAEs | Refractory to standard therapies | I/II | 104 | NCT03941873 |
| ICI combinations with other ICI | |||||
| Durvalumab (PD-L1) plus tremelimumab (CTLA4) | OS | 1st | III | 1504 | NCT03298451 |
| Nivolumab (PD1) plus ipilimumab (CTLA4) | OS | 1st | III | 650 | NCT04039607 |
| Nivolumab (PD1), relatlimab (LAG-3) | ORR | 2nd | II | 250 | NCT04567615 |
| Triplet combinations involving ICI plus targeted therapies | |||||
| Atezolizumab (PD-L1), bevacizumab (VEGFA), tiragolumab (TIGIT), tocilizumab (IL6R), SAR439459 (TGFβ), TPST-1120 (PPARα), RO7247669 (PD1 + LAG-3) | ORR | 1st | Ib/II | 280 | NCT04524871 |
| Pembrolizumab (PD1), quavonlimab (CTLA4), lenvatinib (VEGFR1–3, PDGFR, FGFR1–4, RET) | ORR, DLT, incidence of AEs/SAEs, hepatic AEs, discontinuation due to AEs. | 1st | II | 110 | NCT04740307 |
| Nivolumab (PD1), ipilimumab (CTLA4), cabozantinib (VEGFR1–3, MET, RET) | ORR, incidence of AEs/SAEs | 1st or 2nd | I/II | 1097 | NCT01658878 |
| Novel immunologic targets | |||||
| Voyager V1 (VSV oncolytic virus), cemiplimab (PD1) | ORR | 2nd | II | 152 | NCT04291105 |
| Talimogene laherparepvec (T-VEC, HSV oncolytic virus), pembrolizumab (PD1) | DLT, ORR | 2nd | I/II | 206 | NCT02509507 |
| GNOS-PVO2 (personalized neoantigen), INO-9012 (IL-12), pembrolizumab (PD1) | Incidence of AEs, immunogenicity | 2nd | I/II | 24 | NCT04251117 |
| ET140203 T cells (AFP) | Incidence of AEs, DLTs, RP2D | 3rd+ | I/II | 50 | NCT04502082 |
| ECT204 T cells (GPC3) | Incidence of AEs, DLTs, RP2D | 3rd+ | I/II | 12 | NCT04864054 |
| Other targeted therapies | |||||
| Icaritin (Stem cells) | OS | 1st | III | 200 | NCT03236649 |
| CVM-1118 (Vascular mimicry), sorafenib (VEGFR1–3, PDGFR, RAF kinase, KIT receptor) | ORR | TKI-naïve | II | 40 | NCT03582618 |
| Sorafenib (VEGFR1–3, PDGFR, RAF kinase, KIT receptor), YIV-906 (Unknown) | PFS | 1st | II | 125 | NCT04000737 |
| MTL-CEPBA (C/EBP-alpha transcription factor), sorafenib (VEGFR1–3, PDGFR, RAF kinase, KIT receptor) | ORR, incidence of AEs | TKI-naïve | II | 70 | NCT04710641 |
| ATG-008/CC-223 (mTORC1/2) | ORR, Cmax, AUC, Incidence TEAEs/SAEs | 2nd | II | 75 | NCT03591965 |
| DKN-01 (DKK1), sorafenib (VEGFR1–3, PDGFR, RAF kinase, KIT receptor) | TTP, AEs | 1st | I/II | 70 | NCT03645980 |
| MLN0128 (mTORC1/2) | MTD, TTP | 2nd | I/II | 11 | NCT02575339 |
Note: If multiple studies exist of the same regimen, the latest-phase study is presented. AEs, Adverse events; AFP, alpha-fetoprotein; AUC, Area under the curve; DLT: Dose-limiting toxicity; GPC3, glypican 3; ICI, immune checkpoint inhibitor; MTD, Maximum tolerated dose; mTORC, mammalian target of rapamycin; ORR, objective response rate; PD1, programmed cell death protein 1; PD-L1, programmed death ligand 1; RP2D, Recommended phase 2 dose; SAEs, Severe adverse events; TEAEs, Treatment-emergent adverse events; TKI, tyrosine kinase inhibitor; TTP, Time to progression; VEGFR2, vascular endothelial growth factor receptor 2; VSV, vesicular stomatitis virus.