Recruiting
Phase 1/2
Dual-Target HER2/CEA CAR-NK Cells in Advanced Biliary Tract Cancer
Condition(s) studied
CholangiocarcinomaIntrahepatic CholangiocarcinomaExtrahepatic CholangiocarcinomaGallbladder CarcinomaBiliary Tract Cancer
Investigational drug(s) / intervention(s)
EB-HC01 dual-target CARNK cells: EB-HC01 dual-target CARNK cells
Fludarabine: Fludarabine
Cyclophosphamide: Cyclophosphamide
Study summary
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.
Eligibility
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.
Primary outcome measure(s)
- Dose-Limiting Toxicities — 28 Days
- Treatment-Emergent Adverse Events — 12 months
Trial sites (1)
| Facility | City | Region | Status |
|---|
| Peking University Shenzhen Hospital |
Shenzhen |
Guangdong |
Recruiting |
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