Table 1.
Selected Ongoing Trials of Combination Therapies in aHCCa
| ClinicalTrials.Gov Identifier | Interventions (Mechanism) | Phase, Setting | Primary Outcome | |
|---|---|---|---|---|
| (No. of Patients) | Measures | Study Completion | ||
| ICI-antiangiogenic therapy | ||||
| NCT04770896 (554) | Atezolizumab+lenvatinib/sorafenib vs lenvatinib/sorafenib | III, HCC previously treated with atezolizumab and bevacizumab | OS | Oct. 2024 |
| NCT04560894 (621) | SCT-I10A+SCT510 vs sorafenib | III, aHCC | OS, PFS | Sep. 2024 |
| NCT04523493 (519) | Toripalimab+lenvatinib vs lenvatinib | III, aHCC | OS, PFS | Jan. 2025 |
| NCT04465734 (477) | HLX10+HLX04 vs sorafenib | III, aHCC | OS, PFS | Mar. 2024 |
| NCT04344158 (648) | AK105+anlotinib vs sorafenib | III, aHCC | OS | Dec. 2024 |
| NCT04194775 (525) | CS1003+lenvatinib vs lenvatinib | III, aHCC | PFS, OS | Jun. 2023 |
| NCT03755791 (740) | Atezolizumab+cabozantinib vs sorafenib | III, aHCC | PFS, OS | Dec. 2021 |
| NCT03764293 (510) | SHR-1210+apatinib vs sorafenib | III, aHCC | OS, PFS | Jun. 2022 |
| NCT03794440 (595) | Sintilimab+IBI305 vs sorafenib | III, aHCC | OS, PFS | Dec. 2022 |
| ICI-ICI | ||||
| NCT04720716 (490) | Sintilimab+IBI310 vs sorafenib | III, aHCC | OS, ORR | Dec. 2023 |
| NCT04039607 (634) | Nivolumab+ipilimumab vs sorafenib/lenvatinib | III, aHCC | OS | Jan. 2025 |
| NCT03298451 (1504) | Durvalumab±tremelimuma vs sorafenib | III, aHCC | OS | Apr. 2022 |
| Other combinations | ||||
| NCT03605706 (396) | FOLFOX4+SHR-1210(PD-L1 mAb) vs SHR-1210 | III, aHCC | OS | Dec. 2021 |
| NCT03680508 (42) | TSR-042(PD-1 mAb)+TSR-022(TIM-3 mAb) | II, aHCC | ORR | Oct. 2023 |
| NCT03647163 (40) | Pembrolizumab(PD-1 mAb)+VSV-IFNβ-NIS(Oncolytic virus) | I/II, aHCC | ORR, safety | Jun. 2023 |
| NCT02795429 (89) | PDR001(PD-1 mAb)+INC280(c-Met inhibitor) | Ib/II, aHCC | DLTs, MTD, ORR | Jun. 2021 |
| LRT-systemic therapy | ||||
| NCT04712643 (342) | TACE+atezolizumab + bevacizumab vs TACE | III, untreated HCC | PFS, OS | Feb. 2027 |
| NCT04268888 (522) | TACE/TAE + nivolumab vs TACE/TAE | II/III, intermediated HCC | OS, TTTP | Jun. 2026 |
| NCT04246177 (950) | TACE+lenvatinib+pembrolizumab vs TACE+placebo | III, incurable/non-metastatic HCC | PFS, OS | Dec. 2029 |
| NCT04167293 (116) | SBRT+sintilimab vs sintilimab | III, HCC with PVI after arterially directed therapy | PFS | Oct. 2022 |
| NCT04053985 (206) | TAI+lenvatinib vs lenvatinib | III, aHCC | OS, PFS | Dec. 2022 |
| NCT03905967 (336) | TACE+lenvatinib vs lenvatinib | III, aHCC | OS | Jun. 2023 |
| NCT03778957 (710) | TACE+durvalumab±bevacizumab vs TACE+placebo | III, locoregional HCC not amenable to curative therapy | PFS | Aug. 2024 |
| NCT03775395 (250) | HAIC+lenvatinib vs HAIC+sorafenib | III, aHCC | OS | Dec. 2021 |
Notes: aTrials include the combination of locoregional therapies with systemic therapies.
Abbreviations: OS, overall survival; PFS, progression-free survival;ORR, overall response rate; DLTs, dose limiting toxicities; MTD, maximum tolerated dose; TTTP, time to TACE progression; ICI, immune checkpoint inhibitor; LRT, locoregional therapy; mAb, monoclonal antibody; PD-1, programmed cell death protein 1;PD-L1, programmed death 1 ligand 1; PVI, portal vein invasion; TACE, transarterial chemoembolization; TAE, transarterial embolisation; HAIC, hepatic arterial infusion chemotherapy; TIM-3, T cell immunoglobulin and mucin domain containing-3; SBRT, stereotactic body radiotherapy; TAI, transarterial chemoinfusion; FOLFOX4, fluorouracil, leucovorin, and oxaliplatin; HCC, hepatocellular carcinoma; aHCC, advanced HCC.