Dual-target CLDN18.2/HER2 CAR-NK Cells for Advanced Gastric/GEJ Cancer (DUET-GEJ)

April 18, 2026 updated by: Beijing Biotech

A Phase 1/2, Open-label, Multicenter Study of Allogeneic Dual-target CLDN18.2/HER2 (ERBB2) CAR-NK Cells After Fludarabine/Cyclophosphamide Lymphodepletion in

This example planning study proposes a phase 1/2 evaluation of an allogeneic, cord-blood-derived dual-target CAR-NK product directed against CLDN18.2 and HER2 (ERBB2) in adults with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma after prior standard systemic therapy. CLDN18.2 is selected as the anchor antigen because it has the more disease-specific gastric/GEJ cell-therapy development footprint, while HER2 is retained as the complementary second antigen to address co-expressing or heterogeneous disease. Phase 1 uses a 3+3 dose-escalation design after fludarabine/cyclophosphamide lymphodepletion followed by three intravenous CAR-NK infusions on Days 0, 3, and 7. Phase 2 expansion evaluates the recommended phase 2 dose and preliminary antitumor activity

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This draft is intentionally modeled on current CLDN18.2- and HER2-directed cell-therapy studies on ClinicalTrials.gov and related primary publications. The key strategic choice is that HER2 and ERBB2 are treated as the same target; therefore the meaningful dual-target construct in gastric/GEJ cancer is CLDN18.2 plus HER2. The study is designed as a biomarker-driven, non-randomized phase 1/2 program. In phase 1, patients will receive fludarabine/cyclophosphamide lymphodepletion on Days -5 to -3, followed by three infusions of EB-DT-CAR-NK on Days 0, 3, and 7. A 3+3 dose-escalation structure with three planned dose levels will be used to determine dose-limiting toxicities, maximum tolerated dose, and/or recommended phase 2 dose.

In phase 2, patients will receive the recommended dose on the same schedule in an expansion cohort focused on CLDN18.2-positive gastric/GEJ adenocarcinoma, with prespecified subgroup analyses by HER2 status. The study will assess safety, objective response rate, disease control, durability, survival outcomes, and CAR-NK expansion/persistence. Correlative studies will explore the relationship between baseline CLDN18.2/HER2 expression and clinical outcome.

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:

  • Signed informed consent before any study-specific procedure.
  • Age 18 to 75 years.
  • Histologically confirmed unresectable locally advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
  • Central confirmation of CLDN18.2-positive disease by immunohistochemistry, defined for this draft as membranous CLDN18.2 expression in at least 10% of tumor cells. HER2 testing is required for all subjects; HER2-positive disease is defined as IHC 3+ or IHC 2+/ISH+ using gastric/GEJ testing criteria.
  • Disease progression after at least 2 prior systemic regimens for advanced disease, including a fluoropyrimidine and platinum agent unless contraindicated or not tolerated. If HER2-positive, prior HER2-directed therapy is expected unless unavailable, contraindicated, or not tolerated.
  • At least 1 measurable lesion according to RECIST v1.1.
  • ECOG performance status 0 or 1.
  • Life expectancy of at least 12 weeks.
  • Adequate hematologic, renal, hepatic, pulmonary, and cardiac function.
  • Recovery of prior treatment-related toxicities to Grade 1 or baseline, except alopecia or stable endocrine replacement therapy.
  • Willingness to provide archival tumor tissue or fresh biopsy material if archival tissue is inadequate for central biomarker confirmation.
  • Negative pregnancy test for women of childbearing potential and agreement to use effective contraception during the protocol-defined period

Exclusion Criteria:

  • Prior CLDN18.2-targeted or HER2-targeted genetically modified cell therapy (CAR-T, CAR-NK, TCR-T, or similar).
  • Active or untreated central nervous system metastases or leptomeningeal disease.
  • Active uncontrolled infection, including uncontrolled HBV, HCV, or HIV viremia.
  • Active autoimmune disease requiring systemic immunosuppression.
  • Clinically significant uncontrolled cardiovascular disease, including recent myocardial infarction, unstable angina, uncontrolled arrhythmia, or severe heart failure.
  • Active gastrointestinal perforation, uncontrolled upper GI bleeding, clinically significant bowel obstruction, or unstable gastric ulcer.
  • History of solid-organ transplantation or prior allogeneic hematopoietic stem-cell transplantation with active graft-versus-host disease.
  • Requirement for systemic corticosteroids above physiologic replacement (for example, >10 mg/day prednisone equivalent) within 7 days before lymphodepletion.
  • Pregnancy or breastfeeding.
  • Another active malignancy requiring systemic therapy, except for adequately treated non-melanoma skin cancer, carcinoma in situ, or other protocol-allowed low-risk malignancies.
  • Any medical, psychiatric, or social condition that, in the investigator's judgment, would make study participation unsafe or would interfere with interpretation of study results.

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: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation Cohort
Participants receive fludarabine and cyclophosphamide lymphodepletion on Days -5 to -3, followed by EB-DT-CAR-NK infusions on Days 0, 3, and 7. Three planned dose levels are explored using a 3+3 design.
Biological: EB-DT-CAR-NK
Allogeneic, cord-blood-derived CAR-NK cells engineered to target CLDN18.2 and HER2 (ERBB2). Planned phase 1 dose levels: 2 x 10^6, 4 x 10^6, and 8 x 10^6 cells/kg/infusion. Administered intravenously on Days 0, 3, and 7.
Drug: Fludarabine
Lymphodepleting chemotherapy administered intravenously at 30 mg/m^2/day on Days -5 to -3.
Other Names:
  • FC lymphodepletion regimen
Drug: Cyclophosphamide
Lymphodepleting chemotherapy administered intravenously at 500 mg/m^2/day on Days -5 to -3.
Other Names:
  • FC lymphodepletion regimen
Experimental: Dose Expansion Cohort
Participants receive the recommended phase 2 dose (RP2D) on the same lymphodepletion and infusion schedule. Expansion is centered on CLDN18.2-positive gastric/GEJ adenocarcinoma, with HER2 status captured for exploratory subgroup analysis.
Biological: EB-DT-CAR-NK
Allogeneic, cord-blood-derived CAR-NK cells engineered to target CLDN18.2 and HER2 (ERBB2). Planned phase 1 dose levels: 2 x 10^6, 4 x 10^6, and 8 x 10^6 cells/kg/infusion. Administered intravenously on Days 0, 3, and 7.
Drug: Fludarabine
Lymphodepleting chemotherapy administered intravenously at 30 mg/m^2/day on Days -5 to -3.
Other Names:
  • FC lymphodepletion regimen
Drug: Cyclophosphamide
Lymphodepleting chemotherapy administered intravenously at 500 mg/m^2/day on Days -5 to -3.
Other Names:
  • FC lymphodepletion regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose-limiting toxicities (DLTs)
Time Frame: 28 days
DLTs graded by CTCAE v5.0, with CRS and ICANS graded using ASTCT criteria.
28 days
Determination of MTD
Time Frame: 6 months
Dose-escalation decision based on DLT frequency and overall tolerability across planned cohorts.
6 months
Objective response rate (ORR)
Time Frame: 12 months
Confirmed complete response plus partial response according to RECIST v1.1 in evaluable subjects in the expansion cohort.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 12 months
Time from first infusion to disease progression or death from any cause.
12 months
Overall survival (OS)
Time Frame: 24 months
Time from first infusion to death from any cause.
24 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

April 18, 2026

First Submitted That Met QC Criteria

April 18, 2026

First Posted (Actual)

April 24, 2026

Study Record Updates

Last Update Posted (Actual)

April 24, 2026

Last Update Submitted That Met QC Criteria

April 18, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ESSEN-DUET-GEJ-117

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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