Table 1 Clinical trial targets in esophageal cancer

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]