Esophageal cancer comes in two main forms — squamous cell carcinoma (more common in Asia and Africa) and adenocarcinoma (rising in Western countries, linked to acid reflux and obesity). Both have historically poor outcomes because most patients are diagnosed at an advanced stage.
What's actually going on in research
Checkpoint immunotherapy added to chemotherapy has now improved survival in advanced esophageal cancer and is moving into the curative treatment setting before and after surgery. HER2-targeted therapies are benefiting the subset of adenocarcinomas that overexpress HER2. FGFR and VEGFR inhibitors are being tested in molecular subsets, as the field moves from one-size-fits-all chemotherapy toward precision treatment.
Checkpoint immunotherapy
Combining PD-1 inhibitors with chemotherapy has improved survival in advanced esophageal squamous cell carcinoma and adenocarcinoma, and trials are testing these combinations around surgery.
HER2 targeting
For the 15–20% of esophageal adenocarcinomas that overexpress HER2, antibody-drug conjugates and HER2 bispecifics are showing strong results after standard therapy.
Perioperative strategies
Trials are comparing chemotherapy alone, chemoradiation, and immunotherapy-chemotherapy combinations given before and after surgery to determine the best curative approach.
What to know before you search
Eligibility depends on histologic subtype (squamous vs. adenocarcinoma), HER2 and PD-L1 status, disease stage, and prior treatment history.
What types of trials are currently open
- Treatment trials — Testing new drug combinations or immunotherapy in advanced or metastatic esophageal cancer.
- Perioperative trials — Testing preoperative and postoperative therapy to improve surgical cure rates.
- Endoscopic trials — Evaluating endoscopic resection and ablation for early-stage tumors and Barrett's esophagus.
- Biomarker trials — Identifying HER2, PD-L1, and other markers that guide treatment selection.
- Supportive care trials — Managing swallowing difficulties, nutrition, and treatment side effects.
Recently added Esophageal Cancer trials
Induction Chemo-Immunotherapy + Radiotherapy vs Concurrent Chemoradiotherapy for Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma
This is a prospective, randomized, phase II clinical study in patients with unresectable stage III-IVA esophageal squamous cell carcinoma (ESCC). Eligible patients will be randomly assigned in a 1:1 ratio to two treatment groups. The experimental group will receive 3 cycles of induction therapy with PD-1 antibody plus chemotherapy, followed by radiotherapy, and then maintenance therapy with PD-1 antibody monotherapy. The control group will receive concurrent chemoradiotherapy, followed by maintenance therapy with PD-1 antibody monotherapy. The primary endpoints are the complete response (CR) rate at 3 months after radiotherapy (assessed by investigators) and the 1-year progression-free survival (PFS) rate. Secondary endpoints include overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR), local-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), quality of life, and safety profile.
A Phase 1 Study Evaluating DISP-10 in Participants With Advanced Gastrointestinal Cancers
This is a Phase 1, multicenter, open-label study of DISP-10, a combination therapy consisting of DV-10 (adenovirus) and idecabtagene vicleucel (ide-cel, BCMA-directed chimeric antigen receptor \[CAR\] T), in adult participants with advanced gastrointestinal (GI) cancers. The study will consist of 2 parts: dose-escalation (Part 1) and dose-expansion (Part 2). Part 1 of the study will evaluate the safety and tolerability of increasing dose levels of DISP-10 to establish the recommended dose for expansion (RDE); Part 2 will evaluate the safety and efficacy of DISP-10 in participants treated at the RDE.
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