441 Esophageal Cancer Clinical Trials Recruiting Now (July 2026): Histology, HER2, PD-L1, CLDN18.2

Last updated: July 1, 2026

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Current Clinical Trial Landscape

Active research areas in 2026:

Neoadjuvant chemoimmunotherapy before surgery (multiple Phase 3 trials in ESCC)
Adjuvant nivolumab after neoadjuvant chemoRT (CheckMate-577 established as standard)
ADCs: YL201 (B7-H3), SYS6010, ifinatamab deruxtecan (HER2), sonesitatug vedotin
ctDNA/MRD-guided adjuvant therapy — treat based on residual disease detection
Proton therapy vs photon radiation for reduced toxicity

Standard of care: Locally advanced ESCC: neoadjuvant chemoRT (CROSS) or chemo + surgery, ± adjuvant nivolumab (CheckMate-577). EAC/GEJ: perioperative FLOT ± IO. Metastatic: nivolumab + chemo (CheckMate-648) or pembrolizumab + chemo (KEYNOTE-590). HER2+ GEJ/EAC: trastuzumab + chemo + pembrolizumab.

Recruiting Trials by Treatment Setting

Neoadjuvant / Perioperative (Resectable)

Adding immunotherapy to neoadjuvant chemo or chemoRT — the most active area in esophageal cancer trials:

Chemoimmunotherapy before surgery:
- NCT04821843 - Neoadjuvant treatment modalities in esophageal cancer (Phase 3)
- NCT04821778 - Chemoradiotherapy in esophageal or GEJ cancer (Phase 3)
Adjuvant after surgery:
Radiation approaches:
- NCT03801876 - Proton therapy vs photon radiation for esophageal cancer (Phase 3)
- NCT06676449 - TDLN-sparing RT + IO + chemo in locally advanced ESCC (Phase 3)

Locally Advanced — Definitive Chemoradiation

For patients not undergoing surgery — IO added to definitive chemoRT:

- NCT06964568 - CCRT + PD-1 inhibitor maintenance in locally advanced ESCC (Phase 3)

Metastatic / Recurrent — First-Line

IO + chemo is standard first-line. Trials test novel combinations and ADCs:

Novel IO combinations:
- NCT07221149 - Pumitamig (PD-L1×VEGF bispecific) + chemo in esophageal/GEJ cancer (Phase 3)
- NCT06203600 - Nivolumab added to standard treatment for advanced stomach/esophageal cancer (Phase 3)

Metastatic — Second-Line and Beyond

After first-line IO+chemo failure — ADCs and novel agents:

ADCs:
- NCT06644781 - Ifinatamab deruxtecan (HER2 ADC) in pretreated esophageal/GEJ cancer (Phase 3)
- NCT07431281 - Sonesitatug vedotin + capecitabine ± rilvegostomig in GEJ/gastric (Phase 3)
Other agents:
- NCT07463573 - QLC5508 vs chemo in pretreated ESCC (Phase 3)
- NCT07392892 - PF-08634404 + chemo in esophageal/GEJ cancer (Phase 3)

Showing selected notable trials. View all 441 recruiting interventional trials on ClinicalTrials.gov.

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What esophageal cancer trials are currently recruiting?

There are 441 recruiting interventional trials for esophageal cancer in July 2026 (esophageal-specific filter; the broader EGJ/gastric overlap brings the total closer to 568) including 52 Phase 3 studies. New July 2026 Phase 3 entrants: sonesitatug vedotin (CLDN18.2 ADC) ± rilvegostomig NCT07431281, PARAMUNE nivolumab + standard NCT06203600, Symbiotic-GI-16 PF-08634404 NCT07392892, pumitamig + chemo NCT07221149. Active classes: checkpoint immunotherapy (KEYNOTE-590, CheckMate-648, CheckMate-577 adjuvant), ADCs (YL201, SYS6010, ifinatamab deruxtecan, sonesitatug vedotin — see CLDN18.2 hub + HER2 ADCs hub), rilvegostomig PD-1/TIGIT bispecific, neoadjuvant chemoimmunotherapy, proton therapy, and ctDNA-guided adjuvant strategies.

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