TABLE 4.
Summary of ongoing phase 3 trials of locoregional therapies combined with ICIs in HCC.
| Trial (NCT number) | Population (BCLC stage) | Projected enrolment | Experimental arm | Control arm | Primary endpoint |
|---|---|---|---|---|---|
| RFA combined with ICIs | |||||
| RANT (NCT05277675) | Recurrent HCC after liver resection or RFA (early stage) | 160 | Neoadjuvant therapy (tislelizumab/sintilimab + lenvatinib/bevacizumab) plus RFA | RFA | 1‐year RFS and OS |
| TACE combined with ICIs | |||||
| EMERALD‐1 (NCT03778957) | Not amenable to curative treatment but amenable to TACE (intermediate/advanced stage) | 600 | TACE in combination with durvalumab (arm A) | TACE in combination with placebos (arm C) | PFS (arm B vs. arm C) |
| TACE in combination with durvalumab and bevacizumab (arm B) | |||||
| LEAP‐012 (NCT04246177) | Not amenable to curative treatment but amenable to TACE (intermediate stage) | 950 | cTACE plus pembrolizumab plus lenvatinib | cTACE | OS and PFS |
| TACE‐3 (NCT04268888) | Not amenable to curative treatment but amenable to TACE (intermediate stage) | 522 | DEB‐TACE plus nivolumab | DEB‐TACE | OS |
| CheckMate 74W (NCT04340193) | Beyond Milan and up‐to‐7 criteria and eligible for TACE (intermediate stage) | 765 | TACE plus nivolumab plus ipilimumab | TACE | OS and TTTP (all arm A vs. arm C) |
| TACE plus nivolumab | |||||
| EMERALD‐3 (NCT05301842) | Locoregional HCC not amenable to curative therapy (intermediate stage) | 525 | Tremelimumab, durvalumab, and lenvatinib in combination with TACE (arm A); | TACE (arm C) | PFS (arm A vs. arm C) |
| Tremelimumab and durvalumab in combination with TACE (arm B) | |||||
| NCT04559607 | CNLC stage IIa‐IIIa (intermediate/advanced stage) | 188 | TACE plus camrelizumab plus apatinib | TACE | PFS |
| HAIC combined with ICIs | |||||
| NCT05233358 | Low response or failure to TACE (intermediate and advanced stage) | 176 | HAIC combined with regorafenib and immune checkpoint inhibitors | TACE combined with regorafenib and immune checkpoint inhibitors | PFS |
| NCT05250843 | High‐risk recurrence after resection (intermediate and advanced stage) | 90 | Neoadjuvant therapy with TACE/HAIC and lenvatinib and sintilimab before liver resection | Liver resection | RFS |
Abbreviations: BCLC, Barcelona clinic liver cancer; CNLC, China liver cancer; cTACE, conventional transarterial chemoembolization; DEB‐TACE, TACE with drug‐eluting beads; HAIC, hepatic arterial infusion chemotherapy; ICIs, Immune checkpoint inhibitors; OS, overall survival; PFS, progression‐free survival; RFA, Radiofrequency ablation; RFS, recurrence‐Free survival; TACE, transarterial chemoembolization; TTTP, time to TACE progression.