Dual-Target HER2/CEA CAR-NK Cells in Advanced Biliary Tract Cancer (DUET-BTC)
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
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert 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.
Studietype
Registrering (Antatt)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiekontakt
- Navn: Seni S Lu, Phd
- Telefonnummer: +86 13076790030
- E-post: Seni-Lu@beijing-biotech.com
Studiesteder
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Guangdong
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Shenzhen, Guangdong, Kina, 518036
- Rekruttering
- Peking University Shenzhen Hospital
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Ta kontakt med:
- Zhen J Peng, Phd
- Telefonnummer: +86 13076790039
- E-post: Zhen-Peng@beijing-biotech.com
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
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
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: 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.
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Fludarabin
Cyklofosfamid
EB-HC01 dual-target CARNK cells
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Dose-Limiting Toxicities
Tidsramme: 28 Days
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28 Days
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Treatment-Emergent Adverse Events
Tidsramme: 12 months
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12 months
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Samlet overlevelse
Tidsramme: 24 måneder
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24 måneder
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Objektiv responsrate
Tidsramme: 12 måneder
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12 måneder
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Varighet av svar
Tidsramme: 24 måneder
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24 måneder
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Progresjonsfri overlevelse
Tidsramme: 24 måneder
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24 måneder
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Disease Control Rate
Tidsramme: 12 months
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12 months
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Samarbeidspartnere og etterforskere
Sponsor
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Neoplasmer etter nettsted
- Neoplasmer
- Neoplasmer etter histologisk type
- Neoplasmer i fordøyelsessystemet
- Sykdommer i fordøyelsessystemet
- Galleveissykdommer
- Neoplasmer, kjertel og epitel
- Adenokarsinom
- Karsinom
- Galleblæren sykdommer
- Neoplasmer i galleveiene
- Kolangiokarsinom
- Neoplasmer i galleblæren
- Organiske kjemikalier
- Hydrokarboner
- Fosforamid -sennep
- Nitrogen sennepsforbindelser
- Sennepsforbindelser
- Hydrokarboner, halogenert
- Fosforamider
- Organofosforforbindelser
- Cyklofosfamid
- fludarabin
Andre studie-ID-numre
- ESBI2026-306
Legemiddel- og utstyrsinformasjon, studiedokumenter
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