Non-Small Cell Lung CancerPhase 1/2DUO-NK-NSCLCNCT07467863
Dual-Target CAR-NK Cells Directed Against MSLN, EGFR, or HER2 in Advanced NSCLC
A Phase 1/2 study testing Dual-target CAR-NK cells, Lymphodepleting chemotherapy and Supportive Care in people with Non-Small Cell Lung Cancer and Advanced/Metastatic NSCLC, run by Beijing Biotech at 1 site in China.
Trial summary
This is a two-part, biomarker-guided Phase 1/2 study evaluating the safety, feasibility, and preliminary anti-tumor activity of off-the-shelf dual-target CAR-NK cells in participants with advanced or metastatic NSCLC whose tumors co-express at least two of the following antigens: Mesothelin (MSLN), EGFR, and… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-Small Cell Lung Cancer, Advanced/Metastatic NSCLC
- What is being tested?
- Dual-target CAR-NK cells, 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
- 48 participants
- Where
- 1 siteChina
- Study dates
- 2 Feb 2026to 17 Feb 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 or cytologically confirmed NSCLC that is unresectable Stage IIIB/IIIC or Stage IV, with radiographic progression on or after standard-of-care therapy (including platinum-based chemotherapy and immune checkpoint inhibitor when appropriate).
- At least one measurable lesion per RECIST v1.1.
- Archival tumor tissue available (or willingness to undergo a fresh biopsy) for antigen testing.
- Tumor co-expression of at least two of the following antigens at screening: MSLN, EGFR, HER2/ERBB2.
- Example thresholds: IHC ≥2+ in ≥50% of tumor cells for each required antigen (or an equivalent RNA expression threshold).
- ECOG performance status 0-1.
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- Adequate organ function (hematologic, hepatic, renal) as defined by protocol laboratory limits.
- Life expectancy ≥12 weeks.
- Negative pregnancy test for individuals of childbearing potential; agreement to use effective contraception for the study-defined period.
- Ability to understand and willingness to sign written informed consent.
Who cannot join
- Active, uncontrolled central nervous system (CNS) metastases. Participants with previously treated/stable CNS disease may be eligible if clinically stable and off high-dose corticosteroids.
- Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK, TCR-T) within 3 months, or any prior therapy that in the investigator's judgment increases risk of severe toxicity.
- History of severe cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) with prior therapies.
- Clinically significant interstitial lung disease or pneumonitis requiring systemic steroids, or uncontrolled pulmonary comorbidity that would confound toxicity monitoring.
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, Open-label, Biomarker-guided Study of Dual-target Chimeric Antigen Receptor Natural Killer (CAR-NK) Cells Targeting Mesothelin (MSLN) With EGFR or HER2/ERBB2, or EGFR With HER2/ERBB2, in Participants With Advanced/Metastatic Non-small Cell Lung Cancer (NSCLC)
This is a two-part, biomarker-guided Phase 1/2 study evaluating the safety, feasibility, and preliminary anti-tumor activity of off-the-shelf dual-target CAR-NK cells in participants with advanced or metastatic NSCLC whose tumors co-express at least two of the following antigens: Mesothelin (MSLN), EGFR, and HER2/ERBB2.
Participants will receive lymphodepleting chemotherapy followed by infusion of the CAR-NK product matched to their tumor antigen profile. A data-driven interim assessment will be used to select the most suitable construct for expansion.
Read the detailed description
The study includes Part A (dose escalation) and Part B (dose expansion). In Part A, participants are assigned to one of three dual-target CAR-NK constructs based on tumor antigen co-expression (IHC and/or RNA profiling): MSLN/EGFR, MSLN/HER2, or EGFR/HER2. Dose escalation within each construct follows a standard 3+3 design to identify a recommended Phase 2 dose (RP2D). In Part B, the study expands at the RP2D and may adaptively prioritize the construct demonstrating the most favorable benefit-risk profile (e.g., acceptable safety with early signals of response). Key exploratory objectives include CAR-NK persistence, immune pharmacodynamics, cytokine profiling, and correlations between antigen density and clinical outcomes. This document is an example ClinicalTrials.gov-style registration template for planning purposes only and is not an actual registered study
- Being tested
- Dual-target CAR-NK cells, Lymphodepleting chemotherapy, Supportive Care
- Keywords
- CAR-NK, dual-target, bispecific, Mesothelin, MSLN, EGFR, HER2, ERBB2, adoptive cell therapy, solid tumor, immunotherapy, dose escalation, biomarker-guided
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dual-target CAR-NK cellsBiological
Allogeneic cord-blood-derived NK cells engineered to express a dual-target CAR (tandem OR-gate) and IL-15 for enhanced persistence; includes an inducible safety switch (e.g., iCasp9). Infused intravenously on Day 0 (with optional repeat infusion on Day 7 in expansion, per protocol).
Lymphodepleting chemotherapyDrug
Fludarabine + Cyclophosphamide administered on Days -5, -4, and -3 prior to CAR-NK infusion
Supportive CareOther
Premedication and management per institutional guidelines (e.g., acetaminophen/antihistamine pre-infusion; tocilizumab and corticosteroids per CRS/ICANS management algorithm)
| Study group | Role | What they receive |
|---|---|---|
| EB-DuoNK-MSLN/EGFR | Experimental | Participants with tumors co-expressing MSLN and EGFR (meeting screening thresholds) receive lymphodepletion followed by EB-DuoNK-MSLN/EGFR infusion at the assigned dose level. Receives: Biological: Dual-target CAR-NK cells; Drug: Lymphodepleting chemotherapy; Other: Supportive Care |
| EB-DuoNK-MSLN/HER2 | Experimental | Participants with tumors co-expressing MSLN and HER2/ERBB2 receive lymphodepletion followed by EB-DuoNK-MSLN/HER2 infusion at the assigned dose level. Receives: Biological: Dual-target CAR-NK cells; Drug: Lymphodepleting chemotherapy; Other: Supportive Care |
| EB-DuoNK-EGFR/HER2 | Experimental | Participants with tumors co-expressing EGFR and HER2/ERBB2 receive lymphodepletion followed by EB-DuoNK-EGFR/HER2 infusion at the assigned dose level. Receives: Biological: Dual-target CAR-NK cells; 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)
Measured: 28 Days
Objective response rate (ORR)
Measured: 6 months
Secondary outcomes (3)
Duration of response (DOR) per RECIST v1.1.
Measured: 12 months
Progression-free survival (PFS).
Measured: 12 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 posted12 Mar 2026
- Study start2 Feb 2026
- Primary completion14 Feb 2027 (estimated)
- Study completion17 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies 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
- Parallel groups
- Model description
- Participants are assigned to a construct based on tumor antigen co-expression. Each construct undergoes dose escalation (3+3) to determine RP2D, followed by expansion; an interim assessment may select one construct for larger expansion.
- 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
- NCT07467863
- Sponsor's protocol ID
- EB-CARNK-NSCLC-002
- Acronym
- DUO-NK-NSCLC
- Status last verified
- Mar 2026
- First submitted
- 14 Feb 2026
- Last updated
- 12 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 12 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open-label, Biomarker-guided Study of Dual-target Chimeric Antigen Receptor Natural Killer (CAR-NK) Cells Targeting Mesothelin (MSLN) With EGFR or HER2/ERBB2, or EGFR With HER2/ERBB2, in Participants With Advanced/Metastatic Non-small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT07467863
- Acronym / sponsor ID
- DUO-NK-NSCLC / EB-CARNK-NSCLC-002
- Keywords
- CAR-NK, dual-target, bispecific, Mesothelin, MSLN, EGFR, 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
- 2 Feb 2026 (actual)
- Primary completion
- 14 Feb 2027 (estimated)
- Study completion
- 17 Feb 2028 (estimated)
- First posted
- 12 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 is a two-part, biomarker-guided Phase 1/2 study evaluating the safety, feasibility, and preliminary anti-tumor activity of off-the-shelf dual-target CAR-NK cells in participants with advanced or metastatic NSCLC whose tumors co-express at least two of the following antigens: Mesothelin (MSLN), EGFR, and HER2/ERBB2.
Participants will receive lymphodepleting chemotherapy followed by infusion of the CAR-NK product matched to their tumor antigen profile. A data-driven interim assessment will be used to select the most suitable construct for expansion.
Detailed description
The study includes Part A (dose escalation) and Part B (dose expansion). In Part A, participants are assigned to one of three dual-target CAR-NK constructs based on tumor antigen co-expression (IHC and/or RNA profiling): MSLN/EGFR, MSLN/HER2, or EGFR/HER2. Dose escalation within each construct follows a standard 3+3 design to identify a recommended Phase 2 dose (RP2D). In Part B, the study expands at the RP2D and may adaptively prioritize the construct demonstrating the most favorable benefit-risk profile (e.g., acceptable safety with early signals of response). Key exploratory objectives include CAR-NK persistence, immune pharmacodynamics, cytokine profiling, and correlations between antigen density and clinical outcomes. This document is an example ClinicalTrials.gov-style registration template for planning purposes only and is not an actual registered study
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Participants are assigned to a construct based on tumor antigen co-expression. Each construct undergoes dose escalation (3+3) to determine RP2D, followed by expansion; an interim assessment may select one construct for larger expansion.
| Arm | Type | Receives |
|---|---|---|
| EB-DuoNK-MSLN/EGFR | Experimental | Biological: Dual-target CAR-NK cells, Drug: Lymphodepleting chemotherapy, Other: Supportive CareParticipants with tumors co-expressing MSLN and EGFR (meeting screening thresholds) receive lymphodepletion followed by EB-DuoNK-MSLN/EGFR infusion at the assigned dose level. |
| EB-DuoNK-MSLN/HER2 | Experimental | Biological: Dual-target CAR-NK cells, Drug: Lymphodepleting chemotherapy, Other: Supportive CareParticipants with tumors co-expressing MSLN and HER2/ERBB2 receive lymphodepletion followed by EB-DuoNK-MSLN/HER2 infusion at the assigned dose level. |
| EB-DuoNK-EGFR/HER2 | Experimental | Biological: Dual-target CAR-NK cells, Drug: Lymphodepleting chemotherapy, Other: Supportive CareParticipants with tumors co-expressing EGFR and HER2/ERBB2 receive lymphodepletion followed by EB-DuoNK-EGFR/HER2 infusion at the assigned dose level. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically or cytologically confirmed NSCLC that is unresectable Stage IIIB/IIIC or Stage IV, with radiographic progression on or after standard-of-care therapy (including platinum-based chemotherapy and immune checkpoint inhibitor when appropriate).
- At least one measurable lesion per RECIST v1.1.
- Archival tumor tissue available (or willingness to undergo a fresh biopsy) for antigen testing.
- Tumor co-expression of at least two of the following antigens at screening: MSLN, EGFR, HER2/ERBB2.
- Example thresholds: IHC ≥2+ in ≥50% of tumor cells for each required antigen (or an equivalent RNA expression threshold).
Key exclusion criteria (4 listed)
- Active, uncontrolled central nervous system (CNS) metastases. Participants with previously treated/stable CNS disease may be eligible if clinically stable and off high-dose corticosteroids.
- Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK, TCR-T) within 3 months, or any prior therapy that in the investigator's judgment increases risk of severe toxicity.
- History of severe cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) with prior therapies.
- Clinically significant interstitial lung disease or pneumonitis requiring systemic steroids, or uncontrolled pulmonary comorbidity that would confound toxicity monitoring.
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 cellsAllogeneic cord-blood-derived NK cells engineered to express a dual-target CAR (tandem OR-gate) and IL-15 for enhanced persistence; includes an inducible safety switch (e.g., iCasp9). Infused intravenously on Day 0 (with optional repeat infusion on Day 7 in expansion, per protocol). | Biological | EB-DuoNK-EGFR/HER2, EB-DuoNK-MSLN/EGFR, EB-DuoNK-MSLN/HER2 |
| Lymphodepleting chemotherapyFludarabine + Cyclophosphamide administered on Days -5, -4, and -3 prior to CAR-NK infusion | Drug | EB-DuoNK-EGFR/HER2, EB-DuoNK-MSLN/EGFR, EB-DuoNK-MSLN/HER2 |
| Supportive CarePremedication and management per institutional guidelines (e.g., acetaminophen/antihistamine pre-infusion; tocilizumab and corticosteroids per CRS/ICANS management algorithm) | Other | EB-DuoNK-EGFR/HER2, EB-DuoNK-MSLN/EGFR, EB-DuoNK-MSLN/HER2 |
Primary outcome
Incidence of dose-limiting toxicities (DLTs)
Time frame: 28 Days
Objective response rate (ORR)
Time frame: 6 months
3 secondary outcomes
Duration of response (DOR) per RECIST v1.1.
Time frame: 12 months
Progression-free survival (PFS).
Time frame: 12 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 12 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 Dual-target CAR-NK cells, Lymphodepleting chemotherapy and Supportive Care in people with Non-Small Cell Lung Cancer and Advanced/Metastatic NSCLC, 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 10 inclusion and 4 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 12 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 2 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 12 Mar 2026.