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Dual-Target HER2/CEA CAR-NK Cells in Advanced Biliary Tract Cancer (DUET-BTC)

6. juni 2026 opdateret af: Beijing Biotech

A Phase 1/2, Open-Label, Biomarker-Selected Study of Allogeneic Dual-Target HER2/CEACAM5 Chimeric Antigen Receptor Natural Killer Cells (EB-HC01) in Participants With Unresectable or Metastatic Cholangiocarcinoma and Other Biliary Tract Cancers

This example phase 1/2, open-label, biomarker-selected study evaluates EB-HC01, an allogeneic dual-target CARNK product composed of a 1:1 mixture of HER2-CAR-NK and CEACAM5-CAR-NK cells, in adults with unresectable or metastatic cholangiocarcinoma or other biliary tract cancers after standard therapy. Part A determines safety, dose-limiting toxicities (DLTs), and the recommended phase 2 dose (RP2D) after reduced-intensity lymphodepletion. Part B evaluates preliminary anti-tumor activity, CAR-NK persistence, and biomarker-response associations.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Biliary tract cancers remain highly lethal after progression on gemcitabine/platinum-based therapy, and only a biomarker-defined minority have actionable cell-surface targets.

HER2 has the strongest clinical validation among the antigens under consideration, including active HER2-targeted drug development and prior HER2 CAR-T experience in advanced BTC. CEACAM5 is retained as a complementary second target because it may reduce antigen escape and improve coverage of heterogeneous disease; however, it is treated conservatively because prior CEA-directed cell therapy has shown gastrointestinal and pulmonary toxicity in other solid tumors. EpCAM is not used for enrollment in this example because physiologic expression in the biliary tree may narrow the safety window for a first systemic study. EB-HC01 is designed as an off-the-shelf cord bloodderived NK-cell product manufactured as a fixed 1:1 mixture of HER2-CAR-NK and CEACAM5-CAR-NK cells.

After fludarabine/cyclophosphamide lymphodepletion, participants receive intravenous EB-HC01 on Days 0 and 7 of a 28-day cycle. In Part A, a standard 3+3 doseescalation design evaluates 3 flat-dose levels to identify the RP2D. In Part B, an expansion cohort at RP2D better defines safety and preliminary activity in biomarkerconfirmed dual-positive BTC.

Key correlative studies include central HER2 and CEACAM5 testing, ctDNA analysis, serum CA19-9 and CEA,and serial blood assessments of CAR-NK persistence and cytokine kinetics. EpCAM testing is retained as an exploratory biomarker to inform future protocol amendments but is not used to determine eligibility.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

30

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 or cytologically confirmed unresectable, recurrent, or metastatic intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder carcinoma.
  • Disease progression after at least 1 prior gemcitabine/platinum-containing regimen in the advanced setting; prior durvalumab and prior HER2-targeted therapy are allowed.
  • Central biomarker confirmation of HER2 positivity (IHC 3+ or IHC 2+/ISH+ or ERBB2 amplification) and CEACAM5/CEA positivity (membranous expression in >=20% of viable tumor cells by IHC).
  • At least 1 measurable lesion according to RECIST 1.1.
  • ECOG performance status 0-1.
  • Adequate marrow, renal, hepatic, and cardiac function as defined by the protocol.
  • Resolved biliary obstruction or stable internal/external drainage for >=7 days before lymphodepletion, with no active cholangitis.
  • Life expectancy >=12 weeks.
  • Willingness to provide archival or fresh tumor tissue and serial blood samples for central biomarker testing and correlative studies.
  • Agreement to use protocol-specified contraception

Exclusion Criteria:

  • Prior HER2-directed or CEA-directed gene-modified cell therapy.
  • Untreated or unstable CNS metastases or leptomeningeal disease.
  • Active uncontrolled infection, including uncontrolled cholangitis, sepsis, or clinically significant uncontrolled hepatitis or HIV infection.
  • Ongoing systemic immunosuppression greater than 10 mg/day prednisone equivalent within 7 days before lymphodepletion.
  • Clinically significant interstitial lung disease, uncontrolled heart failure, unstable arrhythmia, or recent myocardial infarction.
  • Child-Pugh B or C liver disease, hepatic encephalopathy, or clinically significant refractory ascites.
  • Prior allogeneic solid organ transplant or allogeneic stemcell transplant.
  • Active autoimmune disease requiring systemic therapy within the previous 2 years.
  • Pregnancy or breastfeeding.
  • Any condition that, in the investigator's judgment, would make lymphodepletion or EB-HC01 infusion unsafe or would interfere with protocol compliance.

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: Ikke-randomiseret
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: EB-HC01 after lymphodepletion
Participants with biomarker-confirmed HER2/CEACAM5-positive advanced biliary tract cancer receive fludarabine plus cyclophosphamide on Days -5 to -3, followed by EB-HC01 intravenously on Days 0 and 7 of each 28-day cycle. Up to 2 cycles are permitted during doseescalation and up to 4 cycles are allowed in expansion in the absence of progression or prohibitive toxicity.
Medicin: Fludarabin
Fludarabin
Medicin: Cyclofosfamid
Cyclofosfamid
Biologisk: EB-HC01 dual-target CARNK cells
EB-HC01 dual-target CARNK cells

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Dose-Limiting Toxicities
Tidsramme: 28 Days
28 Days
Treatment-Emergent Adverse Events
Tidsramme: 12 months
12 months

Sekundære resultatmål

Resultatmål
Tidsramme
Samlet overlevelse
Tidsramme: 24 måneder
24 måneder
Objektiv svarprocent
Tidsramme: 12 måneder
12 måneder
Varighed af svar
Tidsramme: 24 måneder
24 måneder
Progression-fri overlevelse
Tidsramme: 24 måneder
24 måneder
Disease Control Rate
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. oktober 2028

Datoer for studieregistrering

Først indsendt

6. juni 2026

Først indsendt, der opfyldte QC-kriterier

6. juni 2026

Først opslået (Faktiske)

11. juni 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

11. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

6. juni 2026

Sidst verificeret

1. juni 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • ESBI2026-306

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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Kliniske forsøg med Cholangiocarcinom

Kliniske forsøg med Fludarabin

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