Dual-Target CAR-NK Cells for Biomarker-Selected Advanced Colorectal Cancer

March 8, 2026 updated by: Beijing Biotech

A Phase 1/2, Biomarker-Assigned, Open-Label Dose Escalation and Expansion Study of Allogeneic Dual-Target CAR-NK Cells Targeting CEA (CEACAM5) and/or GUCY2C (GCC) With an Exploratory HER2/ERBB2-Positive Cohort in Subjects With Advanced or Metastatic Colorectal Cancer

This Phase 1/2 study evaluates the safety, tolerability, and preliminary anti-tumor activity of an allogeneic dual-target chimeric antigen receptor natural killer (CAR-NK) cell product in adults with advanced or metastatic colorectal cancer (CRC). Participants are assigned to one of three dual-target arms based on tumor antigen co-expression: (1) CEA+GUCY2C, (2) CEA+HER2, or (3) GUCY2C+HER2. Following dose escalation, the most suitable target pair (based on safety, feasibility, and early efficacy/biomarker signals) will be selected for dose expansion.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Colorectal cancer remains a major cause of cancer-related morbidity and mortality. CAR-NK therapy is being explored as a potentially safer, 'off-the-shelf' adoptive cell therapy platform with lower risk of graft-versus-host disease and typically less severe cytokine release than CAR-T in early experiences.

Target selection for solid tumors is limited by tumor heterogeneity and on-target/off-tumor expression. To reduce antigen escape and increase tumor selectivity, this study tests dual-target recognition against CRC-associated antigens: CEA (CEACAM5) and GUCY2C (GCC), with a HER2/ERBB2-positive subset as an exploratory population. GUCY2C is frequently retained in primary and metastatic CRC and is a well-established CRC target antigen. HER2 amplification/overexpression occurs in a minority of metastatic CRC and can be identified by validated IHC/ISH or genomic assays. Biomarker assessment and target-pair selection: Tumor tissue (archival or fresh) is tested by central laboratory immunohistochemistry (IHC) for CEA and GUCY2C, and by HER2 testing per colorectal cancer criteria (IHC with reflex amplification testing as needed). Participants must meet co-expression thresholds for one antigen pair and are assigned accordingly. After Part A (dose escalation), a prespecified selection algorithm will nominate the target pair for expansion using a composite score including DLT rate, feasibility/manufacturing success, ORR/DCR signals, CAR-NK persistence, and evidence of target engagement. Treatment plan: Participants receive lymphodepleting chemotherapy followed by infusion of the assigned dual-target CAR-NK cells. A second infusion in the same cycle may be permitted in selected dose levels if safety criteria are met. Hospitalization/close monitoring is required during the early post-infusion period.

Study Type

Interventional

Enrollment (Estimated)

48

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 confirmed colorectal adenocarcinoma that is unresectable or metastatic and has progressed after, is intolerant to, or is ineligible for standard therapies.
  • Measurable disease per RECIST v1.1 (unless in minimal residual disease (MRD) or post-resection cohorts if a future amendment is planned).
  • Tumor antigen co-expression meeting central lab thresholds for one of the following pairs: CEA+GUCY2C, CEA+HER2, or GUCY2C+HER2.
  • ECOG performance status 0-1.
  • Adequate organ function (hematologic, renal, hepatic, and cardiac) as defined in protocol.
  • Recovered to Grade <=1 from prior therapy-related toxicities (except stable Grade 2 neuropathy or alopecia).
  • Life expectancy >= 12 weeks.
  • Willingness to use effective contraception during study and for a protocol-defined period after cell infusion.

Exclusion Criteria:

  • Active, uncontrolled infection (including uncontrolled HBV/HCV) or known uncontrolled HIV infection.
  • Active CNS metastases that are symptomatic or require escalating steroids. (Stable treated CNS disease may be allowed per protocol.)
  • Prior gene-modified cellular therapy (CAR-T/CAR-NK/TCR-T) within 6 months, or any prior therapy that in the investigator's judgment increases risk of severe toxicity.
  • Clinically significant autoimmune disease requiring systemic immunosuppression within the past 6 months.
  • Concurrent anti-cancer therapy (other than protocol-permitted bridging) during the DLT window.
  • Pregnant or breastfeeding.
  • Significant cardiovascular disease (e.g., recent MI, uncontrolled arrhythmia), uncontrolled pulmonary disease, or other severe comorbidity that would increase risk.
  • Known hypersensitivity to study chemotherapy components (fludarabine/cyclophosphamide) or required supportive medications.
  • Any condition that, in the investigator's opinion, would interfere with study participation, safety monitoring, or interpretation of results.

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: CEA+GUCY2C Dual CAR-NK
CRC with tumor co-expression of CEA (CEACAM5) and GUCY2C (GCC) above prespecified thresholds.
Biological: EB-DUO-CAR-NK-CEA/GCC (IV)
Allogeneic dual-target CAR-NK cells manufactured from cord blood-derived NK cells, genetically engineered to express a tandem (dual-binding) CAR, an IL-15 support element (e.g., membrane-bound IL-15 or IL-15/IL-15R fusion), and an inducible suicide switch
Experimental: CEA+HER2 Dual CAR-NK
CRC with CEA expression and HER2/ERBB2 positivity (HER2 criteria per CRC testing guidance).
Biological: EB-DUO-CAR-NK-CEA/GCC (IV)
Allogeneic dual-target CAR-NK cells manufactured from cord blood-derived NK cells, genetically engineered to express a tandem (dual-binding) CAR, an IL-15 support element (e.g., membrane-bound IL-15 or IL-15/IL-15R fusion), and an inducible suicide switch
Experimental: GUCY2C+HER2 Dual CAR-NK
CRC with GUCY2C expression and HER2/ERBB2 positivity (subset).
Biological: EB-DUO-CAR-NK-CEA/GCC (IV)
Allogeneic dual-target CAR-NK cells manufactured from cord blood-derived NK cells, genetically engineered to express a tandem (dual-binding) CAR, an IL-15 support element (e.g., membrane-bound IL-15 or IL-15/IL-15R fusion), and an inducible suicide switch

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dose-limiting toxicities (DLTs) graded by CTCAE v5.0.
Time Frame: 28 Days
28 Days
Maximum tolerated dose (MTD)
Time Frame: 28 Days
28 Days
Objective response rate (ORR) by RECIST v1.1 in the expansion cohort.
Time Frame: 12 weeks
12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease control rate (DCR)
Time Frame: 24 months
24 months
Progression-free survival (PFS)
Time Frame: 24 months
24 months
Incidence and severity of adverse events (AEs)
Time Frame: 24 months
24 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)

February 1, 2026

Primary Completion (Estimated)

December 21, 2027

Study Completion (Estimated)

December 22, 2028

Study Registration Dates

First Submitted

February 14, 2026

First Submitted That Met QC Criteria

March 8, 2026

First Posted (Actual)

March 10, 2026

Study Record Updates

Last Update Posted (Actual)

March 10, 2026

Last Update Submitted That Met QC Criteria

March 8, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EB-CARNK-CRC-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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