RecruitingPhase 1Phase 2NCT07641036

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

Sponsor

Beijing Biotech

Enrollment

30 participants

Start Date

Mar 2, 2026

Study Type

INTERVENTIONAL

Conditions

Biliary Tract Cancer Cholangiocarcinoma Extrahepatic Cholangiocarcinoma Intrahepatic Cholangiocarcinoma Gallbladder Carcinoma

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

Min Age: 18 Years

Inclusion Criteria10

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 Criteria10

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.