Table 1.
Clinical trial targets in esophageal cancer
| Clinical trial identifier | Trial Drug | Target | Patient population | Phase | Findings | References |
|---|---|---|---|---|---|---|
| NCT02054806 | Pembrolizumab | PD-1 | PD-L1 positive ESCC; EAC; GEAC; GESCC | I | Delayed tumor progression and durable anti-tumor activity with manageable toxicity | [194] |
| NCT02559687 | Pembrolizumab | PD-1 | Metastatic/advanced ESCC; EAC; Siewert type 1 GEAC | II | Durable anti-tumor activity with a manageable safety profile | [195] |
| NCT02564263 | Pembrolizumab | PD-1 | Metastatic/advanced ESCC; EAC; Siewert type 1 GEAC | III | Improved overall survival in combination with chemotherapy drugs (irinotecan, paclitaxel, docetaxel), minimum toxicity | [196] |
| NCT02971956 | Pembrolizumab | PD-1 | Metastatic EAC; Siewert type 1 GEAC | II | Active drug in previously treated esophageal cancer patients with a favorable safety profile | [197] |
| ONO-4538-07/JapicCTI-No.142422 | Nivolumab | PD-1 | Treatment-refractory ESCC; EAC; AC in the cervical or thoracic esophagus | II | Reduced tumor burden with a manageable safety profile | [198] |
| NCT01928394 | Nivolumab + ipilimumab | PD-1/CTLA4 | Chemotherapy-refractory metastatic EAC; GAC; GEAC | I/II | Durable antitumor activity and improved overall survival with a manageable safety profile | [199] |
| NCT02954536 | pembrolizumab + trastuzumab + capecitabine + oxaliplatin | PD-L1 | HER2+ metastatic esophagogastric AC | II | Tumor regression, improved objective response rate with few immune related toxicities | [200] |
| NCT02120911 | Trastuzumab + pertuzumab | HER2 | HER2+ EAC | I/II | Improved overall survival and treatment response | [201] |
| ISRCTN29580179 | Gefitinib | EGFR | ESCC; EAC | III | No improvement in overall survival but possess palliative benefits for patients with a short life expectancy | [202] |
| NCT01336049 | Nimotuzumab + cisplatin + paclitaxel | EGFR | Metastatic ESCC | II | Improved progression-free and overall survival in patients with the unresectable local regional disease and metastatic disease | [203] |
| UMIN000003557 | HLA-A-24-restricted epitope peptides URLC10, CDCA1, KOC1 mixed with montanide | CD8+ T cell | Thoracic ESCC | II | Improved relapse-free survival in patients who showed CD8+ T cell induction to multiple peptides | [204] |
| NCT00682227 | HLA-A24-restricted epitope peptides TTK, LY6K, IMP-3 mixed with montanide | T-cells | ESCC | I | Strong induction of antigen-specific T-cell responses with satisfactory safety and good immunogenicity | [205] |
| UMIN000010158 | adenovirus 5 vector OBP-301 (Telomelysin) | T-cells | EC | I/II | complete response in 2 patients and partial response with tumor regression in 1 patient with manageable tolerance | [206] |
| NCT00917384 | Ramucirumab | VEGFR-2 | Advanced GAC; GEAC | III | Prolonged overall survival and reduced disease progression risk | [207] |
| NCT01170663 | Ramucirumab + paclitaxel | VEGFR-2 | Advanced GAC; GEAC | III | Increased overall survival | [208] |
| NCT01472016 | ABT-700 | c-MET | Advanced GEC | I | MET amplification was more common in treatment-refractory tumors | |
| NCT01611857 | Tivantinib + FOLFOX | c-MET | Metastatic EAC;GEAC; AC of the stomach | I/II | The treatment showed response and progression-free survival with few treatment-related toxicities | [209] |
| NCT00909025 | IMAB362 (Zolbetuximab) | Claudin 18.2 | Advanced GAC; GEAC | I | Well tolerated drug with a favorable safety profile | [210] |
| NCT01630083 | IMAB362 in combination with EOX (Epirubicin, Oxaliplatin, Capecitabine) chemotherapy | Claudin 18.2 | Advanced GAC; GEAC; EAC | II | Prolonged overall survival | [211] |
| NCT02013154 | DKN-01 + Paclitaxel | DKK1 | Refractory or relapsed EAC; GEAC | I | Combination of DKN-01 + Paclitaxel showed tolerance with favorable safety profile | [212] |
| NCT01795768 | AZD4547 | FGFR | Advanced GEAC | II | Inhibited FGFR2 amplification |
[213] (Abstract) |
| NCT00632333 | TTK + URLC10 + KOC1 + VEGFR1 + VEGFR2 with concurrent cisplatin and fluorouracil | HLA-A*2402 | ESCC | I | The combination therapy proved to be well-tolerated with few toxicities and a satisfactory safety profile | [214] |
| NCT01612546 | CRLX101 | DNA Topoisomerase I | Chemotherapy-refracted EAC | II | Exhibited minimal activity with stable disease and favorable toxicity profile | [215] |
Abbreviations: ESCC Esophageal Squamous Cell Carcinoma, EAC Esophageal Adenocarcinoma, GAC Gastric Adenocarcinoma, GEC Gastroesophageal Cancer, GEAC Gastroesophageal Junction Adenocarcinoma, AC Adenocarcinoma; GESCC, gastroesophageal squamous cell carcinoma