Table 1.
Overview of clinical trials with immunotherapies targeting immunosuppressive TME in ESCC.
| Identifier | Drug/Treatment | Target | Ethnicity | Phase | Status | Result | Ref. |
|---|---|---|---|---|---|---|---|
| NCT03189719 (KEYNOTE-590) | Pembrolizumab + CT vs. Placebo + CT (first-line) | PD-1 | Asian and Western | III | Active, not recruiting | Available | (8) |
| NCT03143153 (CheckMate-648) | Nivolumab + Ipilimumab vs. Nivolumab + CT vs. CT (first-line) | PD-1; CTLA-4 | Asian and Western | III | Active, not recruiting | Available | (176) |
| NCT03691090 (ESCORT-1st) | Camrelizumab + CT vs. Placebo + CT (first-line) | PD-1 | Asian | III | Completed | Available | (177) |
| NCT03829969 (JUPITER-06) | Toripalimab + CT vs. Placebo + CT (first-line) | PD-1 | Asian | III | Active, not recruiting | Available | (178) |
| NCT03748134 (ORIENT-15) | Sintilimab + CT vs. Placebo + CT (first-line) | PD-1 | Asian and Western | III | Recruiting | Available | (179) |
| NCT03469557 | Tislelizumab + CT (first-line) | PD-1 | Asian | II | Completed | Available | (180) |
| NCT02564263 (KEYNOTE-181) | Pembrolizumab vs. CT (second-line) | PD-1 | Asian and Western | III | Completed | Available | (9) |
| NCT02569242 (ATTRACTION-3) | Nivolumab vs. CT (second-line) | PD-1 | Asian and Western | III | Completed | Available | (181) |
| NCT03099382 (ESCORT) | Camrelizumab vs. CT (second-line) | PD-1 | Asian | III | Completed | Available | (182) |
| NCT03430843 (RATIONALE-302) | Tislelizumab vs. CT (second-line) | PD-1 | Asian and Western | III | Active, not recruiting | Available | (183) |
| NCT01938612 | Durvalumab monotherapy/Durvalumab + tremelimumab (≥ second-line) | PD-L1; CTLA-4 | Asian | I | Completed | Available | (184) |
| NCT02054806 (KEYNOTE-028) | Pembrolizumab (≥ third-line) | PD-1 | Asian and Western | Ib | Completed | Available | (185) |
| NCT02559687 (KEYNOTE-180) | Pembrolizumab (≥ third-line) | PD-1 | Asian and Western | II | Completed | Available | (186) |
| NCT03792347 (PALACE-1) | Preoperative pembrolizumab + CRT (neoadjuvant therapy) | PD-1 | Asian | Ib | Completed | Available | (187) |
| NCT02743494 (CheckMate-577) | Nivolumab vs. Placebo after surgery (adjuvant therapy) | PD-1 | Asian and Western | III | Active, not recruiting | Available | (188) |
| NCT04210115 (KEYNOTE-975) | Pembrolizumab + dCRT vs. placebo + dCRT | PD-1 | Asian and Western | III | Recruiting | Not available | N/A |
| NCT04435197 (PALACE-2) | Preoperative pembrolizumab + CRT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT04389177 (KEYSTONE-001) | Neoadjuvant pembrolizumab + nCT followed by surgery | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT04807673 (KEYSTONE-002) | Neoadjuvant pembrolizumab + nCT + surgery vs. nCRT + surgery | PD-1 | Asian | III | Recruiting | Not available | N/A |
| NCT05302011 | Neoadjuvant pembrolizumab + nCT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT05130684 | Neoadjuvant nivolumab + nCRT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT03914443 (FRONTiER) | Neoadjuvant nivolumab + nCT | PD-1 | Asian | I | Active, not recruiting | Not available | N/A |
| NCT05213312 | Neoadjuvant nivolumab + nCT vs. nCT | PD-1 | Asian | II/III | Recruiting | Not available | N/A |
| NCT03416244 (RAMONA) | Nivolumab + Ipilimumab vs. Nivolumab | PD-1; CTLA-4 | Western | II | Completed | Not available | N/A |
| NCT04426955 | Camrelizumab + dCRT vs. Placebo + dCRT | PD-1 | Asian | III | Active, not recruiting | Not available | N/A |
| NCT05050760 | Camrelizumab + CT | PD-1 | Asian | N/A | Recruiting | Not available | N/A |
| NCT04741490 | Postoperative camrelizumab + RT | PD-1 | Asian | N/A | Recruiting | Not available | N/A |
| NCT04286958 | Camrelizumab after dCRT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT04767295; NCT05476380 | Neoadjuvant camrelizumab + nCT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT04506138 | Neoadjuvant camrelizumab + nCT | PD-1 | Asian | I/II | Active, not recruiting | Not available | N/A |
| NCT04225364 | Neoadjuvant camrelizumab + nCT | PD-1 | Asian | II | Completed | Not available | N/A |
| NCT05176002 | Neoadjuvant camrelizumab + nRT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT05507411 (WATCHER) | Neoadjuvant camrelizumab + cCRT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT04005170 | Toripalimab + dCRT | PD-1 | Asian | II | Completed | Not available | N/A |
| NCT04848753 | Neoadjuvant toripalimab + nCT vs. Placebo + nCT | PD-1 | Asian | III | Recruiting | Not available | N/A |
| NCT04280822 | Neoadjuvant toripalimab + nCT vs. nCT | PD-1 | Asian | III | Recruiting | Not available | N/A |
| NCT04644250; NCT05424432 | Neoadjuvant toripalimab + nCRT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT04844385 | Neoadjuvant toripalimab + nCT + cCRT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT04177797 | Neoadjuvant toripalimab + nCT | PD-1 | Asian | II | Active, not recruiting | Not available | N/A |
| NCT04804696 | Neoadjuvant toripalimab + nCT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT03783442 | Tislelizumab + CT | PD-1 | Asian | III | Active, not recruiting | Not available | N/A |
| NCT03957590 (RATIONALE-311) | Tislelizumab + dCRT vs. Placebo + dCRT | PD-1 | Asian | III | Active, not recruiting | Not available | N/A |
| NCT05394415 (LATE) | Tislelizumab + CRT for conversion therapy | PD-1 | Asian | I/II | Recruiting | Not available | N/A |
| NCT05520619 (EC-CRT-002) | Tislelizumab + dCRT with maintenance vs. Tislelizumab + dCRT without maintenance | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT04973306 (iCROSS) | Neoadjuvant tislelizumab +nCRT vs. nCRT | PD-1 | Asian | II/III | Recruiting | Not available | N/A |
| NCT05323890; NCT04776590 | Neoadjuvant tislelizumab + nCRT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT04732494 (AdvanTIG-203) | Tislelizumab + Ociperlimab vs. Tislelizumab + Placebo | PD-1; TIGIT | Asian and Western | II | Recruiting | Not available | N/A |
| NCT05495152 | Postoperative sintilimab vs. postoperative follow-up | PD-1 | Asian | III | Active, not recruiting | Not available | N/A |
| NCT04212598 | Sintilimab after dCRT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT03985046 | Sintilimab + CT after dCRT | PD-1 | Asian | II | Active, not recruiting | Not available | N/A |
| NCT05174325; NCT04548440 | Neoadjuvant sintilimab + nCT | PD-1 | Asian | II | Recruiting | Not available | N/A |
| NCT03946969 | Neoadjuvant sintilimab + nCT | PD-1 | Asian | II | Active, not recruiting | Not available | N/A |
| NCT05357846 | Neoadjuvant sintilimab + nCRT vs. nCRT | PD-1 | Asian | III | Not yet recruiting | Not available | N/A |
| NCT04543617 (SKYSCRAPER-07) | Atezolizumab + tiragolumab vs. Atezolizumab + tiragolumab placebo vs. Atezolizumab placebo + tiragolumab placebo | PD-L1; TIGIT | Asian and Western | III | Recruiting | Not available | N/A |
| NCT04540211 (SKYSCRAPER-08) | Atezolizumab + Tiragolumab + CT vs. Placebo + CT | PD-L1; TIGIT | Asian | III | Active, not recruiting | Not available | N/A |
| NCT04550260 (KUNLUN) | Durvalumab + dCRT vs. Placebo + dCRT | PD-L1 | Asian and Western | III | Recruiting | Not available | N/A |
| NCT02520453 | Durvalumab after surgery vs. Placebo after surgery | PD-L1 | Asian | II | Active, not recruiting | Not available | N/A |
| NCT04851132 | Durvalumab + RT | PD-L1 | Asian | N/A | Recruiting | Not available | N/A |
| NCT04568200 | Neoadjuvant durvalumab + nCRT vs. Placebo + nCRT | PD-L1 | Asian | II | Recruiting | Not available | N/A |
| NCT03377400 | Durvalumab + tremelimumab + dCRT | PD-L1; CTLA-4 | Asian | II | Active, not recruiting | Not available | N/A |
| NCT02658214 | Durvalumab + tremelimumab + CT | PD-L1; CTLA-4 | Asian | I | Completed | Not available | N/A |
| NCT03212469 (ABIMMUNE) | Durvalumab + tremelimumab + SBRT | PD-L1; CTLA-4 | Western | I/II | Recruiting | Not available | N/A |
| NCT04140500 | RO7247669 | PD-1; LAG-3 | Asian and Western | I | Recruiting | Not available | N/A |
| NCT03708328 | RO7121661 | PD-1; TIM-3 | Asian and Western | I | Active, not recruiting | Not available | N/A |
| NCT04785820 | RO7247669/RO7121661 vs. Nivolumab | PD-1; LAG-3; TIM-3 | Asian and Western | II | Recruiting | Not available | N/A |
CT, chemotherapy; nCT, neoadjuvant chemotherapy; RT, radiotherapy; nRT, neoadjuvant radiotherapy; CRT, chemoradiotherapy; nCRT, neoadjuvant chemoradiotherapy; dCRT, definitive chemoradiotherapy; cCRT, concurrent chemoradiotherapy; SBRT, stereotactic body radiation therapy; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; CTLA-4, cytotoxic T lymphocyte-associated antigen 4; TIGIT, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain; LAG-3, lymphocyte activation gene-3; TIM-3, T-cell immunoglobulin and mucin domain-containing protein-3; Ref., reference.