Table 2.
Ongoing trials for esophageal cancer with CRT/RT plus ICIs.
| Clinical Trial | Target | Agents | Phase | Treatment Groups | Condition | Primary Endpoints | N |
|---|---|---|---|---|---|---|---|
|
NCT03544736 INEC-study |
PD-1 | Nivolumab | I/II | Cohort A: Nivolumab + palliative RT (20-50 Gy) → Nivolumab Cohort B: Nivolumab + dCRT (RT + CBDCA + PTX) (50.4 Gy) → Nivolumab Cohort C: Nivolumab + Neoadj CRT (RT + CBDCA + PTX) (41.4 Gy) → Nivolumab |
EC/GEJ | Safety | 30 |
| NCT03278626 | PD-1 | Nivolumab | I/II | Nivolumab + dCRT (RT + CBDCA + PTX) (50.4 Gy) | TanyN1-3/T3-4N0M0 ESCC |
Safety | 10 |
|
NCT04210115 KEYNOTE-975 |
PD-1 | Pembrolizumab | III | Pembrolizumab + dCRT (RT + 5FU + LOHP/CDDP) (50 Gy) →Pembrolizumab vs. placebo + dCRT (RT + 5FU + LOHP/CDDP) → placebo |
Unresectable EC/GEJ | OS EFS |
600 |
| NCT02830594 | PD-1 | Pembrolizumab | II | Pembrolizumab + palliative RT | EC/GEJ | Biomarker | 14 |
| NCT02844075 | PD-1 | Pembrolizumab | II | Pembrolizumab+ Neoadj CRT (RT + CBDCA+ taxane) (41.4 Gy) → surgery → Pembrolizumab | T1N1-2/T2-34aN0-2M0 ESCC |
pCR | 18 |
|
NCT03064490 PROCEED |
PD-1 | Pembrolizumab | II | Pembrolizumab+ Neoadj CRT (RT+CBDCA+ PTX) | rE/rGEJ AC | pCR | 38 |
|
NCT04435197 PALACE-2 |
PD-1 | Pembrolizumab | II | Pembrolizumab+ Neoadj CRT (RT + CBDCA + PTX) (41.4 Gy) | cT2-T4aNanyM0 rESCC |
pCR | 143 |
| NCT05103501 | PD-1 | Pembrolizumab | II | CRT → surgery → Pembrolizumab + 5FU + CDDP → Pembrolizumab | Stage II/III ESCC |
DFS | 53 |
| NCT04005170 | PD-1 | Toripalimab | II | Toripalimab + dCRT (RT + CDDP + PTX) (50.4 Gy) → Toripalimab | Unresectable ESCC | cCRR | 42 |
| NCT04844385 | PD-1 | Toripalimab | II | Toripalimab + dCRT (RT + nab-PTX + NDP + CBP) (60.0 Gy) | Unresectable T2-4NanyM0 ESCC |
2-year PFS | 83 |
| NCT04888403 | PD-1 | Toripalimab | II | Toripalimab + Neoadj CRT (RT + nab-PTX + NDP + CBP) (41.4 Gy) | T1-T2N1-N2/T3-4aN0-2M0 ESCC |
pCR | 45 |
| NCT04437212 | PD-1 | Toripalimab | II | Toripalimab + Neoadj CRT (RT + CDDP + PTX) (41.4 Gy) → surgery → Toripalimab | T1-4aN1-2/T3-4aN0M0 ESCC |
MPR | 20 |
| NCT04644250 | PD-1 | Toripalimab | II | Toripalimab + Neoadj CRT (RT + CBDCA + L-PTX) (41.4 Gy) | T3-4aN0-2M0 ESCC | pCR | 32 |
| NCT04177875 | PD-1 | Toripalimab | II | Toripalimab + Neoadj CRT (RT + CDDP + DTX/nab-PTX) (40 Gy) | T2-3N0-1M0 EC |
MPR ORR |
44 |
| NCT04821765 | PD-1 | Tislelizumab | II | Tislelizumab + dCRT (RT + CDDP + nab-PTX) (50-60 Gy) → Tislelizumab | ESCC | LCR | 35 |
| NCT03957590 | PD-1 | Tislelizumab | III | Tislelizumab + dCRT (RT + CDDP + PTX) (50.4 Gy) vs. Placebo + dCRT |
Localized ESCC | PFS | 316 |
| NCT04776590 | PD-1 | Tislelizumab | II | Tislelizumab+ Neoadj CRT (RT + CBDCA + nab-PTX) (41.4 Gy) | rESCC | pCR | 30 |
| NCT05189730 | PD-1 | Tislelizumab | II | Tislelizumab + Neoadj CRT (RT + CBDCA + PTX) (40 Gy) | T2-3N0-1/T1-3N2M0 ESCC |
pCR Safety |
80 |
| NCT04973306 | PD-1 | Tislelizumab | II/III | Tislelizumab + Neoadj CRT (RT + CBDCA + PTX) (41.4 Gy) vs. Neoadj CRT |
cT1b-3N1/cT3-4aN0M0 ESCC |
pCR OS |
176 |
| NCT04512417 | PD-1 | Camrelizumab | II | Camrelizumab + palliative RT vs. Camrelizumab |
EC | PFS | 63 |
| NCT05183958 | PD-1 | Camrelizumab | II | Camrelizumab + CT (PTX + CBDCA/5FU + CDDP/CAP) → palliative RT → Camrelizumab vs. Camrelizumab + CT (PTX + CBDCA/5FU + CDDP/CAP) → Camrelizumab |
ESCC | PFS | 118 |
| NCT04404491 | PD-1 | Camrelizumab | III | Camrelizumab + dCRT (RT + LOHP + CAP) (50-50.4 Gy) vs. Placebo + dCRT |
Stage II-IVA ESCC | Safety PFS |
240 |
| NCT04426955 | PD-1 | Camrelizumab | III | Camrelizumab + dCRT (RT + CDDP + PTX) vs. Placebo + dCRT |
Localized ESCC | PFS | 396 |
| NCT05176002 | PD-1 | Camrelizumab | I/II | Camrelizumab + Neoadj RT | cT1b-2N+/cT3-4aNanyM0 ESCC |
MPR Safety |
26 |
| NCT04286958 | PD-1 | Camrelizumab | II | CRT → Camrelizumab | T1bN+/T2-4N0-2M0 ESCC |
PFS | 40 |
| NCT04741490 | PD-1 | Camrelizumab | NA | Surgery → Camrelizumab + RT (45-55 Gy) | T1-4AN0/T1-4AN +M0 ESCC |
1-year DFS | 20 |
| NCT03940001 | PD-1 | Sintilimab | I | Sintilimab +Neoadj CRT (RT+CBDCA+PTX) (41.4 Gy) | TanyN+/T3-4NanyM0 ESCC |
Safety pCR MPR |
20 |
| NCT04212598 | PD-1 | Sintilimab | II | dCRT/RT → Sintilimab | Stage II/III EC | 2-year DFS | 40 |
| NCT04514835 | PD-1 | Sintilimab | II | dCRT (RT + CAP + CDDP) (50-50.4 Gy) → Sintilimab | T1bN+/T2-T4aN0-2M0 ESCC |
PFS | 44 |
|
NCT04602013 IMCORT |
PD-1 | Sintilimab | II | Sintilimab + dCRT (RT + CDDP + nab-PTX) (60-66 Gy) | Stage II-Iva ESCC | PFS | 53 |
| NCT03490292 | PD-L1 | Avelumab | I/II | Avelumab +Neoadj CRT (RT + CBDCA + PTX) | II/III Stage EC/GEJ | Safety pCR |
24 |
|
NCT03777813 ARION |
PD-L1 | Durvalumab | II | Durvalumab + dCRT (RT + 5FU+ LOHP) (50 Gy) → Durvalumab vs. dCRT |
Unresectable EC | PFS | 120 |
|
NCT04054518 DESC |
PD-L1 | Durvalumab | II | CRT →Durvalumab | EC/GEJ | PFS | 22 |
| NCT04851132 | PD-L1 | Durvalumab | NA | Durvalumab + RT (50.4 Gy) | cT2-4aNanyM0 ESCC |
PFS | 33 |
|
NCT04550260 KUNLUN |
PD-L1 | Durvalumab | III | Durvalumab + dCRT (RT + 5FU/CAP + CDDP) (50-64 Gy) vs. Placebo + dCRT (RT + 5FU + LOHP) (50-64 Gy) |
Stage II-IVA ESCC | PFS | 600 |
|
NCT02735239 Radio |
PD-L1 | Durvalumab | I/II | Cohort D: Durvalumab → Durvalumab + Neoadj CRT (RT + CBDCA + PTX) → surgery | Localized EC/GEJ | Safety | 75 |
| NCT04568200 | PD-L1 | Durvalumab | II | Durvalumab + dCRT (RT + CBDCA + PTX) (41.4 Gy) vs. Placebo + dCRT (RT + CBDCA + PTX) (41.4 Gy) |
T3/T4bNanyM0 ESCC |
pCR | 60 |
| NCT02520453 | PD-L1 | Durvalumab | II | Neoadj CRT → surgery → Durvalumab vs. Neoadj CRT → surgery → Placebo |
T3-4N0/T1-4N1-3M0 ESCC |
DFS | 86 |
|
NCT03437200 CRUCIAL |
PD-1 & CTLA-4 |
Nivolumab & Ipilimumab |
II | Nivolumab + dCRT (RT + 5FU + LOHP) (50 Gy) → Nivolumab vs. Nivolumab + Ipilimumab+ dCRT → Nivolumab +Ipilimumab |
Early stage or locally advanced unresectable EC |
1-year PFS | 130 |
| NCT03604991 | PD-1 & CTLA-4 |
Nivolumab & Ipilimumab |
II/III | Step1: Neoadj CRT (RT + CBDCA + PTX) vs. Neoadj CRT + Nivolumab Step2: adjuvant treatment: Nivolumab vs Nivolumab + Ipilimumab |
T1N1-3/T2-3N0-2M0 rE/rGEJ AC | pCR DFS |
278 |
| NCT03044613 | PD-1 & LAG-3 |
Nivolumab & Relatlimab |
I | Cohort A: Nivolumab → Nivolumab + CRT (RT + CBDCA + PTX) Cohort B: Nivolumab + Relatlimab → Nivolumab + Relatlimab + CRT |
II/III Stage EC/GEJ | Safety | 32 |
| NCT02962063 | PD-L1 & CTLA-4 |
Durvalumab & Tremelimumab |
I/II | Durvalumab + Tremelimumab → Neoadj CRT (RT + CBDCA + PTX) → surgery | TanyN+/T3-4NanyM0 E/GEJ AC |
Safety pCR |
78 |
| NCT03377400 | PD-L1 & CTLA-4 |
Durvalumab & Tremelimumab |
II | Durvalumab/Tremelimumab + dCRT (RT + CDDP + 5FU) → Durvalumab/Tremelimumab | T2-3N0/T1-3N1-3M0 ESCC |
PFS | 40 |
N, Number of patients; CRT, Chemoradiotherapy; RT, Radiotherapy; ICIs, Immune checkpoint inhibitors; dCRT, Definitive chemoradiotherapy; CBDCA, Carboplatin; PTX, Paclitaxel; Neoadj, Neoadjuvant; EC, Esophageal cancer; GEJ, Gastroesophageal junction cancer; ESCC, Esophageal squamous cell carcinoma; 5FU, 5-Fluorouracil plus cisplatin; CDDP, Cisplatin; LOHP, Oxaliplatin; OS, Overall survival; EFS, Event-free Survival; pCR, Complete pathologic response rate; rE, Resectable esophageal cancer; AC, Adenocarcinoma; rGEJ, Resectable gastroesophageal junction cancer; rESCC, Resectable esophageal squamous cell carcinoma; DFS, Disease free survival; cCRR, Clinical complete response rate; nab-PTX, Paclitaxel-albumin; NDP, Nedaplatin; CBP, Capecitabine; PFS, Progression free survival; MPR, Major pathological response rate; L-PTX, Paclitaxel liposome; DTX, Docetaxel; ORR, Objective response rate; LCR, Locoregional control rate.