Table 1.
Overview of ongoing phase III clinical trials on immunotherapy in esophageal cancer as identified on clinicaltrials.gov. (Search August 30th 2021: “esophageal cancer”, “phase III”, “recruiting”, “not yet recruiting”, “active, not recruiting”. Only recruiting phase II/III studies have been included.)
| Registration number clinicaltrails.gov (name trial) | Phase | Treatment | Target (agent) | Patient population | Location of participating sites | |
|---|---|---|---|---|---|---|
| Single agent immunotherapy | NCT03748134 (ORIENT-15) | III | CT + sintilimab CT + placebo | PD-1 (sintilimab) | unresectable or metastatic ESCC | Globally |
| NCT03777657 | III | CT + tislelizumab CT + placebo | PD-1 (tislelizumab) | unresectable or metastatic gastric or GEJ adenocarcinoma | Globally | |
| NCT03783442 | III | CT + tislelizumab CT + placebo | PD-1 (tislelizumab) | unresectable or metastatic ESCC | Globally | |
| NCT03829969 | III | CT + toripalimab CT + placebo | PD-1 (toripalimab) | unresectable or metastatic ESCC | China | |
| NCT03957590 | III | dCRT + tislelizumab dCRT + placebo | PD-1 (tislelizumab) | unresectable ESCC | China | |
| NCT04210115 (KEYNOTE-975) | III | dCRT + pembrolizumab dCRT + placebo | PD-1 (pembrolizumab) | unresectable EAC or ESCC | Globally | |
| NCT04280822 | III | nCT + adjuvant toripalimab nCT | PD-1 (toripalimab) | resectable ESCC | China | |
| NCT04404491 | III | nCRT + adjuvant camrelizumab nCRT + placebo | PD-1 (camrelizumab) | ESCC with local recurrence after surgery | China | |
| NCT04426955 | III | dCRT + camrelizumab dCRT + placebo | PD-1 (camrelizumab) | unresectable ESCC | China | |
| NCT04540211 (SKYSCRAPER-08) | III | CT + tiragolumab + atelizumab CT + placebo | TIGIT (tiragolumab) PD-L1 (atelizumab) | unresectable or metastatic ESCC | Multiple countries in Asia | |
| NCT04543617 (SKYSCRAPER-07) | III | tiragolumab + atelizumab tiragolumab placebo + atelizumab tiragolumab placebo + atelizumab placebo | TIGIT (tiragolumab) PD-L1 (atelizumab | unresectable ESCC without progression after dCRT | Globally | |
| NCT04550260 (KUNLUN) | III | dCRT + durvalumab dCRT + placebo | PD-L1 (durvalumab) | unresectable ESCC | Globally | |
| NCT04807673 (KEYSTONE-002) | III | nCT + neoadjuvant pembrolizumab + adjuvant pembrolizumab nCT | PD-1 (pembrolizumab) | resectable ESCC | China | |
| NCT04821778 | III | dCRT + anti-PD-1/PD-L1 or nimotuzumab dCRT | HER1 (nimotuzumab) PD-1 or PD-L1 (not reported) | unresectable ESCC | China | |
| NCT04821843 | III | nCT + adjuvant anti-PD-1/PD-L1 or nimotuzumab and CT nCRT + adjuvant anti-PD-1/PD-L1 or nimotuzumab and CT | HER1 (nimotuzumab) PD-1 or PD-L1 (not reported) | resectable ESCC | China | |
| NCT04848753 | III | nCT + neoadjuvant toripalimab nCT + placebo | PD-1 (toripalimab) | resectable ESCC | China | |
| Combination therapy | NCT02872116 (Checkmate 649) | III | nivolumab + ipilimumab* | PD-1 (nivolumab) CTLA-4 (ipilimumab) | unresectable or metastastic non-HER2-positive adenocarcinoma of the esophagus, GEJ or stomach | Globally |
| NCT03604991 | II/III | nCRT + adjuvant nivolumab and ipilimumab nCRT + adjuvant nivolumab nCRT + neoadjuvant nivolumab + adjuvant nivolumab and ipilimumab nCRT + neoadjuvant nivolumab + adjuvant nivolumab | PD-1 (nivolumab) CTLA-4 (ipilimumab) | resectable adenocarcinoma esophagus or GEJ | USA | |
| NCT03615326 (KEYNOTE 811) | III | CT + pembrolizumab + trastuzumab CT + placebo + trastuzumab | PD-1 (pembrolizumab) HER2 (trastuzumab) | unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma | Globally | |
| NCT04499924 (MOUNTAINEER-02) | II/III | CT + tucatinib + trastuzumab + ramucirumab CT + tucatinib placebo + trastuzumab placebo + ramucirumab CT + tucatinib + trastuzumab placebo + ramucirumab | HER2 (tucatinib) HER2 (trastuzumab) VEGFR-2 (ramucirumab) | unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma | Globally | |
| NCT04704934 (DESTINY-Gastric04) | III | trastuzumab deruxtecan ramucirumab + paclitaxel | antibody–drug conjugate (trastuzumab deruxtecan) tyrosine kinase inhibitor (remucirumab) | unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma with progression after anti-HER2 therapy | Globally | |
| NCT04879368 (INTEGRATEIIb) | III | regorafenib + nivolumab CT | tyrosine kinase inhibitor (regorafenib) PD-1 (nivolumab) | metastatic AC or undifferentiated carcinoma of the GEJ or stomach | Globally | |
| NCT04949256 | III | pembrolizumab + lenvatinib + CT pembrolizumab + CT | PD-1 (pembrolizumab) tyrosine kinase inhibitor (lenvatinib) | metastatic ESCC | Globally |
CT chemotherapy, dCRT definitive chemoradiotherapy, EAC esophageal adenocarcinoma, EGFR epidermal growth factor receptor, ESCC esophageal squamous cell carcinoma, GEJ gastro-esophageal junction, HER2 human epidermal growth factor receptor 2, ITIM immunoreceptor tyrosine-based inhibitory motif, nCRT neoadjuvant chemoradiotherapy, nCT neoadjuvant chemotherapy, PD-1 programmed cell death protein 1, PD-L1 programmed cell death protein ligand 1, RT radiotherapy, TIGIT T cell immunoreceptor with immunoglobin and ITIM domain, VEGF vascular endothelial growth factor receptor
*Single treatment arm of which the full results [41] are not yet available; results of other study arms have been published[26]