Dual-Target HER2/CEA CAR-NK Cells in Advanced Biliary Tract Cancer (DUET-BTC)

June 6, 2026 updated by: Beijing Biotech

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Fludarabine
Fludarabine
Drug: Cyclophosphamide
Cyclophosphamide
Biological: EB-HC01 dual-target CARNK cells
EB-HC01 dual-target CARNK cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dose-Limiting Toxicities
Time Frame: 28 Days
28 Days
Treatment-Emergent Adverse Events
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival
Time Frame: 24 months
24 months
Objective Response Rate
Time Frame: 12 months
12 months
Duration of Response
Time Frame: 24 months
24 months
Progression-Free Survival
Time Frame: 24 months
24 months
Disease Control Rate
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2026

Primary Completion (Estimated)

March 14, 2027

Study Completion (Estimated)

October 17, 2028

Study Registration Dates

First Submitted

June 6, 2026

First Submitted That Met QC Criteria

June 6, 2026

First Posted (Actual)

June 11, 2026

Study Record Updates

Last Update Posted (Actual)

June 11, 2026

Last Update Submitted That Met QC Criteria

June 6, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ESBI2026-306

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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