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

May 31, 2026 updated by: Beijing Biotech

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background and target-selection logic. Esophageal adenocarcinoma shares biomarker biology with GEJ adenocarcinoma. In the current public development landscape, CLDN18.2 and HER2 are the two most clinically actionable candidates for a first esophageal adenocarcinoma dual-target CAR-NK concept.

This example therefore advances a CLDN18.2/HER2 tandem-target product and treats EGFR as a pre-specified exploratory biomarker, not as the primary CAR target in version 1.

Investigational product. EBNK-1822H2 is a hypothetical off-the-shelf NK-cell product derived from cord blood and engineered with a tandem CAR recognizing CLDN18.2 and HER2, together with a persistence-support module (for example, membrane-bound IL-15) and an inducible caspase-9 safety switch. This is an example investigational product description for protocol-drafting purposes only.

Study structure. Phase 1 uses an open-label dose-escalation design after fludarabine/cyclophosphamide lymphodepletion to identify the maximum tolerated dose (MTD) and recommended phase 2 dose/schedule (RP2D/RP2S). Phase 2 expands at the selected regimen in three biomarker-defined strata: (1) CLDN18.2-positive/HER2-negative, (2) HER2-positive/CLDN18.2-low or negative, and (3) dual-positive disease. Participants receive one intravenous infusion on Day 0; a protocol-defined repeat infusion on Day 21 may be allowed in the expansion portion if there is no DLT or uncontrolled grade 3+ immune toxicity.

Correlative program. Screening includes central or local assessment of CLDN18.2 and HER2, with EGFR captured prospectively at baseline and, when feasible, at progression. Correlative studies include ctDNA response, cytokine profiling, CAR-NK persistence, tumor microenvironment markers, and antigen-pattern analyses to inform future multi-target program evolution.

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EBNK-1822H2 after lymphodepletion
Participants receive fludarabine and cyclophosphamide lymphodepletion followed by intravenous infusion of allogeneic dual-target CLDN18.2/HER2 CAR-NK cells on Day 0. A protocol-defined repeat infusion on Day 21 may be permitted in dose expansion if safety criteria are met.
Biological: 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.
Other Names:
  • Dual-target CAR-NK; EBNK-1822H2
Drug: Fludarabine
Lymphodepletion backbone
Other Names:
  • Fludara
Drug: Cyclophosphamide
Lymphodepletion backbone
Other Names:
  • Cytoxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dose-limiting toxicities (DLTs)
Time Frame: 28 days
28 days
Incidence and severity of treatment-emergent adverse events
Time Frame: 12 months
12 months
Recommended phase 2 dose
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Objective response rate (ORR) by RECIST v1.1
Time Frame: 12 months
12 months
Disease control rate (DCR) by RECIST v1.1
Time Frame: 12 months
12 months
Duration of response
Time Frame: 12 Months
12 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2026

Primary Completion (Estimated)

March 14, 2027

Study Completion (Estimated)

March 17, 2028

Study Registration Dates

First Submitted

May 25, 2026

First Submitted That Met QC Criteria

May 31, 2026

First Posted (Actual)

June 3, 2026

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

May 31, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EBNK-EAC-1822H2-116

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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