Clinical trial · Interventional
Dual-Target HER2/CEA CAR-NK Cells in Advanced Biliary Tract Cancer
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (5)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Biliary Tract Cancer | Malignant Biliary Tract Neoplasm | ALIAS | 0.90 |
| Cholangiocarcinoma | Cholangiocarcinoma | ONTOLOGY_EXACT | 0.98 |
| Extrahepatic Cholangiocarcinoma | Extrahepatic Cholangiocarcinoma | ONTOLOGY_EXACT | 0.98 |
| Gallbladder Carcinoma | Gallbladder Carcinoma | ONTOLOGY_EXACT | 0.98 |
| Intrahepatic Cholangiocarcinoma | Intrahepatic Cholangiocarcinoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| EB-HC01 dual-target CARNK cells | Biological | — | UNRESOLVED |
| Fludarabine | Drug | Fludarabine | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- EB-HC01 after lymphodepletion
- description
- 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.
- interventionNames
- Biological: EB-HC01 dual-target CARNK cells
- Drug: Fludarabine
- Drug: Cyclophosphamide
Primary outcomes (2)
- measure
- Dose-Limiting Toxicities
- timeFrame
- 28 Days
- measure
- Treatment-Emergent Adverse Events
- timeFrame
- 12 months
Secondary outcomes (5)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (0)
Data not yet available