Dual-Target CLDN18.2/HER2 CAR-NK Cells for Advanced Esophageal Adenocarcinoma
A Phase 1/2, Open-Label, Biomarker-Selected Study of Allogeneic Dual-Target CLDN18.2/HER2 Chimeric Antigen Receptor Natural Killer Cells (EBNK-1822H2) in Adults With Relapsed, Refractory, or Metastatic Esophageal Adenocarcinoma
Beijing Biotech
36 participants
Mar 2, 2026
INTERVENTIONAL
Conditions
Summary
This example study evaluates the safety, feasibility, cellular kinetics, and preliminary anti-tumor activity of EBNK-1822H2, an illustrative allogeneic cord blood-derived dual-target CAR-NK cell product directed against CLDN18.2 and HER2, in adults with relapsed/refractory or metastatic esophageal adenocarcinoma after standard therapy. The study uses dose escalation followed by biomarker-defined expansion and prospectively records EGFR expression as an exploratory biomarker of antigen escape.
Eligibility
Inclusion Criteria11
- Histologically confirmed esophageal adenocarcinoma or Siewert I/II gastroesophageal junction adenocarcinoma judged biologically consistent with esophageal adenocarcinoma, unresectable/recurrent/metastatic, and not amenable to curative therapy.
- Disease progressed after at least 1 prior systemic regimen for advanced disease, or the participant is intolerant of / ineligible for standard therapy. Biomarker-directed therapy must have been received or deemed inappropriate/unavailable where standard in the local setting.
- At least 1 measurable lesion by RECIST v1.1.
- Evidence of at least one selected target: CLDN18.2-positive by validated IHC (example threshold: membranous staining in
- ≥75% of tumor cells with moderate/strong intensity or protocol-specified central threshold), and/or HER2-positive by IHC 3+ or IHC 2+/ISH-amplified disease.
- ECOG performance status 0-1.
- Adequate marrow, renal, hepatic, pulmonary, and cardiac function per protocol laboratory thresholds.
- Life expectancy ≥12 weeks.
- Resolution of clinically significant prior-therapy toxicities to grade ≤1 (except alopecia or stable endocrinopathies).
- Willingness to provide archival tumor tissue and to undergo fresh biopsy when safely feasible.
- Negative pregnancy test for participants of childbearing potential and agreement to protocol-defined contraception.
Exclusion Criteria11
- Esophageal squamous cell carcinoma or non-adenocarcinoma histology.
- Known active CNS metastases or leptomeningeal disease; previously treated stable CNS disease may be allowed only if asymptomatic and off escalating steroids per protocol.
- Prior gene-modified cellular therapy within 12 weeks, or another investigational therapy likely to confound interpretation of safety or efficacy.
- Active uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV viremia, sepsis, or clinically significant opportunistic infection.
- Ongoing systemic immunosuppressive therapy above physiologic steroid replacement.
- Active autoimmune disease requiring systemic treatment within 2 years.
- Clinically significant interstitial lung disease/pneumonitis, uncontrolled cardiovascular disease, or left ventricular ejection fraction <50%.
- Active gastrointestinal perforation, uncontrolled bleeding, or clinically significant mucosal ulceration that would increase study-treatment risk.
- Prior solid organ transplant or active graft-versus-host disease.
- Pregnant or breastfeeding.
- Another active malignancy requiring systemic therapy, except protocol-permitted low-risk cancers.
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Interventions
Illustrative allogeneic cord blood-derived NK-cell product engineered to recognize CLDN18.2 and HER2.
Lymphodepletion backbone
Lymphodepletion backbone
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07622940