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

31. maj 2026 opdateret af: 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.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

36

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

  • Kina
    • Guangdong
      • Shenzhen, Guangdong, Kina, 518036
        • Rekruttering
        • Peking University Shenzhen Hospital
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Biologisk: 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.
Andre navne:
  • Dual-target CAR-NK; EBNK-1822H2
Medicin: Fludarabine
Lymphodepletion backbone
Andre navne:
  • Fludara
Medicin: Cyclophosphamide
Lymphodepletion backbone
Andre navne:
  • Cytoxan

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Forekomst af dosisbegrænsende toksiciteter (DLTs)
Tidsramme: 28 dage
28 dage
Incidence and severity of treatment-emergent adverse events
Tidsramme: 12 months
12 months
Recommended phase 2 dose
Tidsramme: 6 months
6 months

Sekundære resultatmål

Resultatmål
Tidsramme
Objektiv responsrate (ORR) vurderet efter RECIST v1.1
Tidsramme: 12 måneder
12 måneder
Disease control rate (DCR) by RECIST v1.1
Tidsramme: 12 months
12 months
Duration of response
Tidsramme: 12 Months
12 Months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Beijing Biotech

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

2. marts 2026

Primær færdiggørelse (Anslået)

14. marts 2027

Studieafslutning (Anslået)

17. marts 2028

Datoer for studieregistrering

Først indsendt

25. maj 2026

Først indsendt, der opfyldte QC-kriterier

31. maj 2026

Først opslået (Faktiske)

3. juni 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

3. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

31. maj 2026

Sidst verificeret

1. maj 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • EBNK-EAC-1822H2-116

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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Kliniske forsøg med Recurrent or Metastatic Esophageal Adenocarcinoma

Kliniske forsøg med EBNK-1822H2 dual-target CLDN18.2/HER2 CAR-NK cells

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

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Betingelser

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Sponsor / samarbejdspartnere

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