Colorectal Cancer MetastaticPhase 1/2NCT07462650
Dual-Target CAR-NK Cells for Biomarker-Selected Advanced Colorectal Cancer
A Phase 1/2 study testing EB-DUO-CAR-NK-CEA/GCC (IV) in people with Colorectal Cancer Metastatic and Adenocarcinoma of Colon, run by Beijing Biotech at 1 site in China.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer Metastatic, Adenocarcinoma of Colon
- What is being tested?
- EB-DUO-CAR-NK-CEA/GCC (IV)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2026to 22 Dec 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036
Zhen J Peng, Phd, +8613076790039, Zhen-Peng@beijing-biotech.com
About this study
Official title: 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.
Read the 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.
- Being tested
- EB-DUO-CAR-NK-CEA/GCC (IV)
- Keywords
- CAR-NK, Dual-target CAR, CEACAM5, CEA, GUCY2C, GCC, HER2, ERBB2, Solid tumor immunotherapy, Allogeneic NK cells, Adoptive cell therapy
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EB-DUO-CAR-NK-CEA/GCC (IV)Biological
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
| Study group | Role | What they receive |
|---|---|---|
| CEA+GUCY2C Dual CAR-NK | Experimental | CRC with tumor co-expression of CEA (CEACAM5) and GUCY2C (GCC) above prespecified thresholds. Receives: Biological: EB-DUO-CAR-NK-CEA/GCC (IV) |
| CEA+HER2 Dual CAR-NK | Experimental | CRC with CEA expression and HER2/ERBB2 positivity (HER2 criteria per CRC testing guidance). Receives: Biological: EB-DUO-CAR-NK-CEA/GCC (IV) |
| GUCY2C+HER2 Dual CAR-NK | Experimental | CRC with GUCY2C expression and HER2/ERBB2 positivity (subset). Receives: Biological: EB-DUO-CAR-NK-CEA/GCC (IV) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs) graded by CTCAE v5.0.
Measured: 28 Days
Maximum tolerated dose (MTD)
Measured: 28 Days
Objective response rate (ORR) by RECIST v1.1 in the expansion cohort.
Measured: 12 weeks
Secondary outcomes (3)
Incidence and severity of adverse events (AEs)
Measured: 24 months
Disease control rate (DCR)
Measured: 24 months
Progression-free survival (PFS)
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2026
- Study start1 Feb 2026
- Primary completion21 Dec 2027 (estimated)
- Study completion22 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Beijing BiotechThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Part A: 3+3 dose-escalation in each biomarker-defined target-pair arm. Part B: expansion cohort in the selected target pair at RP2D (one or more expansions may be opened based on Part A results).
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07462650
- Sponsor's protocol ID
- EB-CARNK-CRC-101
- Status last verified
- Mar 2026
- First submitted
- 14 Feb 2026
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07462650
- Acronym / sponsor ID
- EB-CARNK-CRC-101
- Keywords
- CAR-NK, Dual-target CAR, CEACAM5, CEA, GUCY2C, GCC, HER2, ERBB2
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Beijing BiotechIndustry (pharma, biotech, devices)
- Study start
- 1 Feb 2026 (actual)
- Primary completion
- 21 Dec 2027 (estimated)
- Study completion
- 22 Dec 2028 (estimated)
- First posted
- 10 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Part A: 3+3 dose-escalation in each biomarker-defined target-pair arm. Part B: expansion cohort in the selected target pair at RP2D (one or more expansions may be opened based on Part A results).
| Arm | Type | Receives |
|---|---|---|
| CEA+GUCY2C Dual CAR-NK | Experimental | Biological: EB-DUO-CAR-NK-CEA/GCC (IV)CRC with tumor co-expression of CEA (CEACAM5) and GUCY2C (GCC) above prespecified thresholds. |
| CEA+HER2 Dual CAR-NK | Experimental | Biological: EB-DUO-CAR-NK-CEA/GCC (IV)CRC with CEA expression and HER2/ERBB2 positivity (HER2 criteria per CRC testing guidance). |
| GUCY2C+HER2 Dual CAR-NK | Experimental | Biological: EB-DUO-CAR-NK-CEA/GCC (IV)CRC with GUCY2C expression and HER2/ERBB2 positivity (subset). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Biological | CEA+GUCY2C Dual CAR-NK, CEA+HER2 Dual CAR-NK, GUCY2C+HER2 Dual CAR-NK |
Primary outcome
Incidence of dose-limiting toxicities (DLTs) graded by CTCAE v5.0.
Time frame: 28 Days
Maximum tolerated dose (MTD)
Time frame: 28 Days
Objective response rate (ORR) by RECIST v1.1 in the expansion cohort.
Time frame: 12 weeks
3 secondary outcomes
Incidence and severity of adverse events (AEs)
Time frame: 24 months
Disease control rate (DCR)
Time frame: 24 months
Progression-free survival (PFS)
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing EB-DUO-CAR-NK-CEA/GCC (IV) in people with Colorectal Cancer Metastatic and Adenocarcinoma of Colon, run by Beijing Biotech at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Seni S Lu, Phd (+86 13076790030, Seni-Lu@beijing-biotech.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (DLTs) graded by CTCAE v5.0. (time frame: 28 Days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2026.