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
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Seni S Lu, Phd
- Numéro de téléphone: +86 13076790030
- E-mail: Seni-Lu@beijing-biotech.com
Lieux d'étude
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Guangdong
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Shenzhen, Guangdong, Chine, 518036
- Recrutement
- Peking University Shenzhen Hospital
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Contact:
- Zhen J Peng, Phd
- Numéro de téléphone: +86 13076790039
- E-mail: Zhen-Peng@beijing-biotech.com
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-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
La description
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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: 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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Fludarabine
Cyclophosphamide
EB-HC01 dual-target CARNK cells
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
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Dose-Limiting Toxicities
Délai: 28 Days
|
28 Days
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Treatment-Emergent Adverse Events
Délai: 12 months
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12 months
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Mesures de résultats secondaires
Mesure des résultats |
Délai |
|---|---|
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La survie globale
Délai: 24mois
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24mois
|
|
Taux de réponse objective
Délai: 12 mois
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12 mois
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Durée de la réponse
Délai: 24mois
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24mois
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Survie sans progression
Délai: 24 mois
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24 mois
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Disease Control Rate
Délai: 12 months
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12 months
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Collaborateurs et enquêteurs
Parrainer
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Tumeurs par site
- Tumeurs
- Tumeurs par type histologique
- Tumeurs du système digestif
- Maladies du système digestif
- Maladies des voies biliaires
- Tumeurs, glandulaires et épithéliales
- Adénocarcinome
- Carcinome
- Maladies de la vésicule biliaire
- Tumeurs des voies biliaires
- Cholangiocarcinome
- Tumeurs de la vésicule biliaire
- Produits chimiques organiques
- Hydrocarbures
- Moutards phosphoramides
- Composés de moutarde d'azote
- Composés moutarde
- Hydrocarbures, halogénés
- Phosphoramides
- Composés organophosphores
- Cyclophosphamide
- fludarabine
Autres numéros d'identification d'étude
- ESBI2026-306
Informations sur les médicaments et les dispositifs, documents d'étude
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