Dual-Target HER2/CEA CAR-NK Cells in Advanced Biliary Tract Cancer

NCT07641036 | Recruiting Phase 1 DMC

• 1 other identifier: ESBI2026-306
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cholangiocarcinoma; Intrahepatic Cholangiocarcinoma; Extrahepatic Cholangiocarcinoma; Gallbladder Carcinoma; Biliary Tract Cancer

Keywords

CAR-NK; dual-target cell therapy; HER2; ERBB2; CEA; CEACAM5; cholangiocarcinoma; biliary tract cancer; allogeneic; off-the-shelf; adoptive cell therapy

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicities

  28 Days

• Treatment-Emergent Adverse Events

  12 months

Secondary Outcomes (5)

• Objective Response Rate

  12 months

• Disease Control Rate

  12 months

• Duration of Response

  24 months

• Progression-Free Survival

  24 months

• Overall Survival

  24 months

Study Arms (1)

EB-HC01 after lymphodepletion

EXPERIMENTAL

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.

Biological: EB-HC01 dual-target CARNK cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

EB-HC01 dual-target CARNK cells BIOLOGICAL

EB-HC01 dual-target CARNK cells

EB-HC01 after lymphodepletion

Fludarabine DRUG

Fludarabine

EB-HC01 after lymphodepletion

Cyclophosphamide DRUG

Cyclophosphamide

EB-HC01 after lymphodepletion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma; Gallbladder Neoplasms; Biliary Tract Neoplasms

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two-part, open-label, single-group study. Part A uses a 3+3 dose-escalation design across 3 flat-dose levels (1 x10\^8, 3 x 10\^8, and 1 x 10\^9 total CAR-NK cells per infusion, delivered as a 1:1 mixture of HER2-CAR-NK and CEACAM5-CAR-NK cells). All participants receive lymphodepletion on Days -5 to -3 and EB-HC01 on Days 0 and 7 of each 28-day cycle. Part B is an expansion cohort at RP2D to better define safety and preliminary efficacy.

Study Record Dates

• First Submitted: June 6, 2026
• First Posted: June 11, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): October 17, 2028
• Last Updated: June 11, 2026

Record last verified: 2026-06

Locations

CN (1)