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

NCT07622940 | Recruiting Phase 1 DMC

• 1 other identifier: EBNK-EAC-1822H2-116
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Recurrent or Metastatic Esophageal Adenocarcinoma; Biomarker-selected CLDN18.2-positive and/or HER2-positive Disease

Keywords

CAR-NK; Allogeneic NK cells; Cellular immunotherapy; CLDN18.2; HER2 (ERBB2); EGFR (exploratory biomarker); Esophageal adenocarcinoma; Gastroesophageal junction adenocarcinoma; Dose escalation; Dose expansion

Outcome Measures

Primary Outcomes (3)

• Incidence of dose-limiting toxicities (DLTs)

  28 days

• Incidence and severity of treatment-emergent adverse events

  12 months

• Recommended phase 2 dose

  6 months

Secondary Outcomes (3)

• Objective response rate (ORR) by RECIST v1.1

  12 months

• Disease control rate (DCR) by RECIST v1.1

  12 months

• Duration of response

  12 Months

Study Arms (1)

EBNK-1822H2 after lymphodepletion

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

EBNK-1822H2 dual-target CLDN18.2/HER2 CAR-NK cells BIOLOGICAL

Illustrative allogeneic cord blood-derived NK-cell product engineered to recognize CLDN18.2 and HER2.

Also known as: Dual-target CAR-NK; EBNK-1822H2

EBNK-1822H2 after lymphodepletion

Fludarabine DRUG

Lymphodepletion backbone

Also known as: Fludara

EBNK-1822H2 after lymphodepletion

Cyclophosphamide DRUG

Lymphodepletion backbone

Also known as: Cytoxan

EBNK-1822H2 after lymphodepletion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Adenocarcinoma Of Esophagus

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

shan S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Masking is not used because this is an early-phase adoptive cell therapy study requiring real-time safety monitoring, dose-escalation decisions, and close coordination of cell-product logistics.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, multicenter, biomarker-selected, single-arm study. Phase 1 uses dose escalation of EBNK-1822H2 after fludarabine/cyclophosphamide lymphodepletion to identify the MTD and/or RP2D/RP2S. Phase 2 expands the selected regimen in biomarker-defined cohorts (CLDN18.2-positive, HER2-positive, or dual-positive). EGFR status is collected prospectively for exploratory analyses but does not determine armassignment.

Study Record Dates

• First Submitted: May 25, 2026
• First Posted: June 3, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): March 17, 2028
• Last Updated: June 3, 2026

Record last verified: 2026-05

Locations

CN (1)