Breast Cancer (Locally Advanced or Metastatic)Phase 1/2DUAL-NK-BCNCT07486089
Dual-Target CAR-NK Cells for Advanced Breast Cancer (HER2+ and TNBC)
A Phase 1/2 study testing Dual-target CAR-NK cells (EB-DT-CAR-NK), Lymphodepleting chemotherapy and Supportive care in people with Breast Cancer (Locally Advanced or Metastatic) and HER2-positive Breast Cancer, run by Beijing Biotech at 1 site in China.
Trial summary
This study tests the safety and preliminary anti-tumor activity of an investigational dual-target chimeric antigen receptor natural killer (CAR-NK) cell therapy in adults with advanced breast cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Breast Cancer (Locally Advanced or Metastatic), HER2-positive Breast Cancer, Triple-Negative Breast Cancer (TNBC)
- What is being tested?
- Dual-target CAR-NK cells (EB-DT-CAR-NK), Lymphodepleting chemotherapy and Supportive care
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 2 Feb 2026to 17 Mar 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 breast carcinoma that is locally advanced, unresectable, or metastatic.
- Disease subtype: HER2-positive breast cancer or triple-negative breast cancer (TNBC).
- Progression after, intolerance to, or ineligibility for standard therapies appropriate for the disease subtype and line of therapy.
- At least one measurable lesion per RECIST v1.1.
- Tumor antigen assessment available (fresh or archival): expression of at least one candidate target antigen (HER2/ERBB2, MUC1, or ROR1). For TNBC, mesothelin assessment may be performed for exploratory analyses.
- ECOG performance status 0-1.
Show all 12Show fewer
- Adequate organ function (example thresholds): ANC ≥ 1.0 x 10^9/L; platelets ≥ 75 x 10^9/L; hemoglobin
- 8 g/dL; AST/ALT ≤ 3x ULN (≤ 5x with liver metastases); total bilirubin ≤ 1.5x ULN; creatinine clearance
- 50 mL/min.
- Left ventricular ejection fraction (LVEF) ≥ 45% and no uncontrolled cardiac arrhythmia.
- Negative pregnancy test for participants of childbearing potential; agreement to use effective contraception during study treatment and for 6 months after last CAR-NK infusion.
- Ability to understand and willingness to sign informed consent.
Who cannot join
- Active, untreated central nervous system (CNS) metastases or leptomeningeal disease. Patients with treated CNS metastases may be eligible if clinically stable for ≥ 4 weeks and off high-dose steroids.
- Prior gene-modified cellular therapy (e.g., CAR-T or CAR-NK) within 6 months or unresolved grade ≥ 2 toxicity from prior cellular therapy.
- Clinically significant active autoimmune disease requiring systemic immunosuppression (physiologic steroid replacement permitted).
- Uncontrolled infection, including uncontrolled HBV, HCV, or HIV infection (controlled infections may be eligible per investigator).
- History of severe hypersensitivity to fludarabine or cyclophosphamide.
- Pregnant or breastfeeding.
- Concurrent participation in another interventional study that could confound safety or efficacy assessments.
- Any condition that, in the investigator's judgment, would make the participant unsuitable for the study (e.g., uncontrolled comorbidity, inability to comply with protocol procedures).
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: Phase 1/2, Biomarker-guided, Open-label Study of Allogeneic Dual-target CAR-NK Cells Directed Against HER2/ERBB2, MUC1, and/or ROR1 in Patients With Advanced or Metastatic Breast Cancer (Including HER2-positive and Triple-negative Disease).
This study tests the safety and preliminary anti-tumor activity of an investigational dual-target chimeric antigen receptor natural killer (CAR-NK) cell therapy in adults with advanced breast cancer. After a tumor antigen assessment (HER2/ERBB2, MUC1, ROR1, and in some TNBC cases mesothelin), each participant will receive the most suitable dual-target CAR-NK product for their tumor profile, following short-course lymphodepleting chemotherapy.
Read the detailed description
Natural killer (NK) cells can recognize and kill abnormal cells as part of the innate immune system. CAR engineering can enhance NK-cell recognition of tumor-associated antigens and may improve anti-tumor activity in solid tumors. This is a two-part, first-in-program study. Part A uses dose escalation to identify a safe and feasible dose of a dual-target CAR-NK cell product. Part B evaluates preliminary efficacy in biomarker-defined expansion cohorts for HER2-positive breast cancer and triple-negative breast cancer (TNBC).
Target selection is biomarker-guided. A fresh or archival tumor sample is tested by immunohistochemistry (IHC) for HER2/ERBB2, MUC1, and ROR1 expression. Participants are assigned to one of three dual-target CAR-NK constructs based on a predefined algorithm prioritizing highest and most homogeneous target expression. In TNBC, mesothelin testing may be performed to support an exploratory sub-cohort.
All participants receive lymphodepleting chemotherapy (fludarabine + cyclophosphamide) before CAR-NK infusion. The CAR-NK product is an allogeneic, cryopreserved NK-cell therapy engineered to express a dual-specific CAR and an inducible safety switch; the product is administered intravenously.
- Conditions
- Breast Cancer (Locally Advanced or Metastatic), HER2-positive Breast Cancer, Triple-Negative Breast Cancer (TNBC)
- Being tested
- Dual-target CAR-NK cells (EB-DT-CAR-NK), Lymphodepleting chemotherapy, Supportive care
- Keywords
- CAR-NK; dual targeting, doptive cellular immunotherapy, HER2 / ERBB2, MUC1, ROR1, mesothelin, solid tumor, biomarker-guided cohort assignment, Lymphodepletion, fludarabine, cyclophosphamide
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dual-target CAR-NK cells (EB-DT-CAR-NK)Biological
Also called EB-DT-CAR-NK (Essen Biotech Dual-Target CAR-NK)
Route: IV infusion. Schedule: single infusion on Day 0; optional second infusion on Day 7 in the absence of dose-limiting toxicity (DLT) and with adequate clinical status.
Lymphodepleting chemotherapyDrug
Also called Fludarabine (Fludara®)
fludarabine (Days -5 to -3) and cyclophosphamide (Days -5 to -4), prior to CAR-NK infusion.
Supportive careOther
Also called Cyclophosphamide (Cytoxan®)
Premedication per institutional standard (e.g., acetaminophen and antihistamine).
Tumor lysis and infection prophylaxis per institutional guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation (Part A) | Experimental | Advanced/metastatic breast cancer with measurable disease and expression of at least one target antigen (HER2, MUC1, or ROR1). Participants receive lymphodepletion followed by a single infusion of dual-target CAR-NK (construct chosen by antigen profile). Receives: Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK); Drug: Lymphodepleting chemotherapy; Other: Supportive care |
| Expansion Cohort A (HER2/MUC1) | Experimental | HER2-positive breast cancer (HER2 IHC 3+ or IHC 2+ with ISH amplification) with MUC1 expression; receives HER2/MUC1 dual-target CAR-NK at RP2D. Receives: Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK); Drug: Lymphodepleting chemotherapy; Other: Supportive care |
| Expansion Cohort B (HER2/ROR1) | Experimental | HER2-positive breast cancer or HER2-low disease with high ROR1 expression; receives HER2/ROR1 dual-target CAR-NK at RP2D. Receives: Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK); Drug: Lymphodepleting chemotherapy; Other: Supportive care |
| Expansion Cohort C (MUC1/ROR1; TNBC) | Experimental | Triple-negative breast cancer with MUC1 and/or ROR1 expression; receives MUC1/ROR1 dual-target CAR-NK at RP2D. Exploratory TNBC sub-cohort: mesothelin-positive TNBC may be analyzed separately. Receives: Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK); Drug: Lymphodepleting chemotherapy; Other: Supportive care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs)
Incidence of dose-limiting toxicities (DLTs) (including cytokine release syndrome and neurotoxicity) graded by CTCAE v5.0 and ASTCT consensus criteria for CRS/ICANS
Measured: 28 Days
Safety profile
Safety profile by type, frequency, severity, and relatedness of treatment-emergent adverse events (AEs) and serious AEs.
Measured: 12 months
Recommended Phase 2 Dose
Recommended Phase 2 Dose (RP2D) based on DLTs, overall safety, and biologic activity (CAR-NK expansion/persistence).
Measured: 56 days
Secondary outcomes (5)
Objective response rate (ORR) by RECIST v1.1 (and iRECIST, if immunotherapy response patterns are suspected).
Measured: 12 months
Disease control rate (DCR)
Disease control rate (DCR) (CR+PR+SD)
Measured: 12 months
Duration of response (DoR).
Measured: 24 months
Progression-free survival (PFS)
Measured: 24 months
Overall survival (OS)
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 posted20 Mar 2026
- Study start2 Feb 2026
- Primary completion14 Feb 2027 (estimated)
- Study completion17 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer (Locally Advanced or Metastatic)Studies 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
- Sequential
- Model description
- Part A: 3+3 dose-escalation across 3 planned dose levels. Part B: biomarker-guided, non-randomized expansion cohorts based on tumor antigen expression with cohort-specific Simon two-stage stopping rules for futility.
- Masking
- None (open label)
- Enrolment
- 60 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
- NCT07486089
- Sponsor's protocol ID
- EB-CARNK-BC01
- Acronym
- DUAL-NK-BC
- Status last verified
- Mar 2026
- First submitted
- 17 Mar 2026
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2, Biomarker-guided, Open-label Study of Allogeneic Dual-target CAR-NK Cells Directed Against HER2/ERBB2, MUC1, and/or ROR1 in Patients With Advanced or Metastatic Breast Cancer (Including HER2-positive and Triple-negative Disease).
- ClinicalTrials.gov ID
- NCT07486089
- Acronym / sponsor ID
- DUAL-NK-BC / EB-CARNK-BC01
- Conditions
- Breast Cancer (Locally Advanced or Metastatic), HER2-positive Breast Cancer, Triple-Negative Breast Cancer (TNBC)
- Keywords
- CAR-NK; dual targeting, doptive cellular immunotherapy, HER2 / ERBB2, MUC1, ROR1, mesothelin, solid tumor, biomarker-guided cohort assignment
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Beijing BiotechIndustry (pharma, biotech, devices)
- Study start
- 2 Feb 2026 (actual)
- Primary completion
- 14 Feb 2027 (estimated)
- Study completion
- 17 Mar 2028 (estimated)
- First posted
- 20 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 study tests the safety and preliminary anti-tumor activity of an investigational dual-target chimeric antigen receptor natural killer (CAR-NK) cell therapy in adults with advanced breast cancer. After a tumor antigen assessment (HER2/ERBB2, MUC1, ROR1, and in some TNBC cases mesothelin), each participant will receive the most suitable dual-target CAR-NK product for their tumor profile, following short-course lymphodepleting chemotherapy.
Detailed description
Natural killer (NK) cells can recognize and kill abnormal cells as part of the innate immune system. CAR engineering can enhance NK-cell recognition of tumor-associated antigens and may improve anti-tumor activity in solid tumors. This is a two-part, first-in-program study. Part A uses dose escalation to identify a safe and feasible dose of a dual-target CAR-NK cell product. Part B evaluates preliminary efficacy in biomarker-defined expansion cohorts for HER2-positive breast cancer and triple-negative breast cancer (TNBC).
Target selection is biomarker-guided. A fresh or archival tumor sample is tested by immunohistochemistry (IHC) for HER2/ERBB2, MUC1, and ROR1 expression. Participants are assigned to one of three dual-target CAR-NK constructs based on a predefined algorithm prioritizing highest and most homogeneous target expression. In TNBC, mesothelin testing may be performed to support an exploratory sub-cohort.
All participants receive lymphodepleting chemotherapy (fludarabine + cyclophosphamide) before CAR-NK infusion. The CAR-NK product is an allogeneic, cryopreserved NK-cell therapy engineered to express a dual-specific CAR and an inducible safety switch; the product is administered intravenously.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Part A: 3+3 dose-escalation across 3 planned dose levels. Part B: biomarker-guided, non-randomized expansion cohorts based on tumor antigen expression with cohort-specific Simon two-stage stopping rules for futility.
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation (Part A) | Experimental | Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK), Drug: Lymphodepleting chemotherapy, Other: Supportive careAdvanced/metastatic breast cancer with measurable disease and expression of at least one target antigen (HER2, MUC1, or ROR1). Participants receive lymphodepletion followed by a single infusion of dual-target CAR-NK (construct chosen by antigen profile). |
| Expansion Cohort A (HER2/MUC1) | Experimental | Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK), Drug: Lymphodepleting chemotherapy, Other: Supportive careHER2-positive breast cancer (HER2 IHC 3+ or IHC 2+ with ISH amplification) with MUC1 expression; receives HER2/MUC1 dual-target CAR-NK at RP2D. |
| Expansion Cohort B (HER2/ROR1) | Experimental | Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK), Drug: Lymphodepleting chemotherapy, Other: Supportive careHER2-positive breast cancer or HER2-low disease with high ROR1 expression; receives HER2/ROR1 dual-target CAR-NK at RP2D. |
| Expansion Cohort C (MUC1/ROR1; TNBC) | Experimental | Biological: Dual-target CAR-NK cells (EB-DT-CAR-NK), Drug: Lymphodepleting chemotherapy, Other: Supportive careTriple-negative breast cancer with MUC1 and/or ROR1 expression; receives MUC1/ROR1 dual-target CAR-NK at RP2D. Exploratory TNBC sub-cohort: mesothelin-positive TNBC may be analyzed separately. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed breast carcinoma that is locally advanced, unresectable, or metastatic.
- Disease subtype: HER2-positive breast cancer or triple-negative breast cancer (TNBC).
- Progression after, intolerance to, or ineligibility for standard therapies appropriate for the disease subtype and line of therapy.
- At least one measurable lesion per RECIST v1.1.
- Tumor antigen assessment available (fresh or archival): expression of at least one candidate target antigen (HER2/ERBB2, MUC1, or ROR1). For TNBC, mesothelin assessment may be performed for exploratory analyses.
Key exclusion criteria (8 listed)
- Active, untreated central nervous system (CNS) metastases or leptomeningeal disease. Patients with treated CNS metastases may be eligible if clinically stable for ≥ 4 weeks and off high-dose steroids.
- Prior gene-modified cellular therapy (e.g., CAR-T or CAR-NK) within 6 months or unresolved grade ≥ 2 toxicity from prior cellular therapy.
- Clinically significant active autoimmune disease requiring systemic immunosuppression (physiologic steroid replacement permitted).
- Uncontrolled infection, including uncontrolled HBV, HCV, or HIV infection (controlled infections may be eligible per investigator).
- History of severe hypersensitivity to fludarabine or cyclophosphamide.
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 |
|---|---|---|
| Dual-target CAR-NK cells (EB-DT-CAR-NK)Also: EB-DT-CAR-NK (Essen Biotech Dual-Target CAR-NK)Route: IV infusion. Schedule: single infusion on Day 0; optional second infusion on Day 7 in the absence of dose-limiting toxicity (DLT) and with adequate clinical status. | Biological | Dose Escalation (Part A), Expansion Cohort A (HER2/MUC1), Expansion Cohort B (HER2/ROR1), Expansion Cohort C (MUC1/ROR1; TNBC) |
| Lymphodepleting chemotherapyAlso: Fludarabine (Fludara®)fludarabine (Days -5 to -3) and cyclophosphamide (Days -5 to -4), prior to CAR-NK infusion. | Drug | Dose Escalation (Part A), Expansion Cohort A (HER2/MUC1), Expansion Cohort B (HER2/ROR1), Expansion Cohort C (MUC1/ROR1; TNBC) |
| Supportive careAlso: Cyclophosphamide (Cytoxan®)Premedication per institutional standard (e.g., acetaminophen and antihistamine). Tumor lysis and infection prophylaxis per institutional guidelines. | Other | Dose Escalation (Part A), Expansion Cohort A (HER2/MUC1), Expansion Cohort B (HER2/ROR1), Expansion Cohort C (MUC1/ROR1; TNBC) |
Primary outcome
Incidence of dose-limiting toxicities (DLTs)
Time frame: 28 Days
Incidence of dose-limiting toxicities (DLTs) (including cytokine release syndrome and neurotoxicity) graded by CTCAE v5.0 and ASTCT consensus criteria for CRS/ICANS
Safety profile
Time frame: 12 months
Safety profile by type, frequency, severity, and relatedness of treatment-emergent adverse events (AEs) and serious AEs.
Recommended Phase 2 Dose
Time frame: 56 days
Recommended Phase 2 Dose (RP2D) based on DLTs, overall safety, and biologic activity (CAR-NK expansion/persistence).
5 secondary outcomes
Objective response rate (ORR) by RECIST v1.1 (and iRECIST, if immunotherapy response patterns are suspected).
Time frame: 12 months
Disease control rate (DCR)
Time frame: 12 months
Duration of response (DoR).
Time frame: 24 months
Progression-free survival (PFS)
Time frame: 24 months
Overall survival (OS)
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 20 Mar 2026.
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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 Dual-target CAR-NK cells (EB-DT-CAR-NK), Lymphodepleting chemotherapy and Supportive care in people with Breast Cancer (Locally Advanced or Metastatic) and HER2-positive Breast Cancer, 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 12 inclusion and 8 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 20 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) (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 20 Mar 2026.