Ireland
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Recruiting Phase 1/2

Dual-Target CLDN18.2/HER2 CAR-NK Cells for Advanced Esophageal Adenocarcinoma

NCT07622940 · tracked via the Priya Life Science China tracker
Phase
Phase 1/2
Started
2026-03-02
Last updated
2026-06-03

Condition(s) studied

Recurrent or Metastatic Esophageal AdenocarcinomaBiomarker-selected CLDN18.2-positive and/or HER2-positive Disease

Investigational drug(s) / intervention(s)

EBNK-1822H2 dual-target CLDN18.2/HER2 CAR-NK cellsFludarabine →Cyclophosphamide →

EBNK-1822H2 dual-target CLDN18.2/HER2 CAR-NK cells: Illustrative allogeneic cord blood-derived NK-cell product engineered to recognize CLDN18.2 and HER2.

Fludarabine: Lymphodepletion backbone

Cyclophosphamide: Lymphodepletion backbone

Study 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

Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Inclusion Criteria: * 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 Criteria: * 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.

Primary outcome measure(s)

  • Incidence of dose-limiting toxicities (DLTs) — 28 days
  • Incidence and severity of treatment-emergent adverse events — 12 months
  • Recommended phase 2 dose — 6 months

Trial sites (1)

FacilityCityRegionStatus
Peking University Shenzhen Hospital Shenzhen Guangdong Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07622940 on ClinicalTrials.gov ↗ ← All trials in China