Advanced Gastric AdenocarcinomaPhase 1/2DUET-GEJNCT07551362
Dual-target CLDN18.2/HER2 CAR-NK Cells for Advanced Gastric/GEJ Cancer
A Phase 1/2 study testing EB-DT-CAR-NK, Fludarabine and Cyclophosphamide in people with Advanced Gastric Adenocarcinoma and Advanced Gastroesophageal Junction Adenocarcinoma, run by Beijing Biotech at 1 site in China.
Trial summary
This example planning study proposes a phase 1/2 evaluation of an allogeneic, cord-blood-derived dual-target CAR-NK product directed against CLDN18.2 and HER2 (ERBB2) in adults with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma after prior standard systemic therapy. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Gastric Adenocarcinoma, Advanced Gastroesophageal Junction Adenocarcinoma
- What is being tested?
- EB-DT-CAR-NK, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 2 Mar 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
- Signed informed consent before any study-specific procedure.
- Age 18 to 75 years.
- Histologically confirmed unresectable locally advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
- Central confirmation of CLDN18.2-positive disease by immunohistochemistry, defined for this draft as membranous CLDN18.2 expression in at least 10% of tumor cells. HER2 testing is required for all subjects; HER2-positive disease is defined as IHC 3+ or IHC 2+/ISH+ using gastric/GEJ testing criteria.
- Disease progression after at least 2 prior systemic regimens for advanced disease, including a fluoropyrimidine and platinum agent unless contraindicated or not tolerated. If HER2-positive, prior HER2-directed therapy is expected unless unavailable, contraindicated, or not tolerated.
- At least 1 measurable lesion according to RECIST v1.1.
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- ECOG performance status 0 or 1.
- Life expectancy of at least 12 weeks.
- Adequate hematologic, renal, hepatic, pulmonary, and cardiac function.
- Recovery of prior treatment-related toxicities to Grade 1 or baseline, except alopecia or stable endocrine replacement therapy.
- Willingness to provide archival tumor tissue or fresh biopsy material if archival tissue is inadequate for central biomarker confirmation.
- Negative pregnancy test for women of childbearing potential and agreement to use effective contraception during the protocol-defined period
Who cannot join
- Prior CLDN18.2-targeted or HER2-targeted genetically modified cell therapy (CAR-T, CAR-NK, TCR-T, or similar).
- Active or untreated central nervous system metastases or leptomeningeal disease.
- Active uncontrolled infection, including uncontrolled HBV, HCV, or HIV viremia.
- Active autoimmune disease requiring systemic immunosuppression.
- Clinically significant uncontrolled cardiovascular disease, including recent myocardial infarction, unstable angina, uncontrolled arrhythmia, or severe heart failure.
- Active gastrointestinal perforation, uncontrolled upper GI bleeding, clinically significant bowel obstruction, or unstable gastric ulcer.
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- History of solid-organ transplantation or prior allogeneic hematopoietic stem-cell transplantation with active graft-versus-host disease.
- Requirement for systemic corticosteroids above physiologic replacement (for example, >10 mg/day prednisone equivalent) within 7 days before lymphodepletion.
- Pregnancy or breastfeeding.
- Another active malignancy requiring systemic therapy, except for adequately treated non-melanoma skin cancer, carcinoma in situ, or other protocol-allowed low-risk malignancies.
- Any medical, psychiatric, or social condition that, in the investigator's judgment, would make study participation unsafe or would interfere with interpretation of study 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, +86 13076790039, Zhen-Peng@beijing-biotech.com
About this study
Official title: A Phase 1/2, Open-label, Multicenter Study of Allogeneic Dual-target CLDN18.2/HER2 (ERBB2) CAR-NK Cells After Fludarabine/Cyclophosphamide Lymphodepletion in
This example planning study proposes a phase 1/2 evaluation of an allogeneic, cord-blood-derived dual-target CAR-NK product directed against CLDN18.2 and HER2 (ERBB2) in adults with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma after prior standard systemic therapy. CLDN18.2 is selected as the anchor antigen because it has the more disease-specific gastric/GEJ cell-therapy development footprint, while HER2 is retained as the complementary second antigen to address co-expressing or heterogeneous disease. Phase 1 uses a 3+3 dose-escalation design after fludarabine/cyclophosphamide lymphodepletion followed by three intravenous CAR-NK infusions on Days 0, 3, and 7. Phase 2 expansion evaluates the recommended phase 2 dose and preliminary antitumor activity
Read the detailed description
This draft is intentionally modeled on current CLDN18.2- and HER2-directed cell-therapy studies on ClinicalTrials.gov and related primary publications. The key strategic choice is that HER2 and ERBB2 are treated as the same target; therefore the meaningful dual-target construct in gastric/GEJ cancer is CLDN18.2 plus HER2. The study is designed as a biomarker-driven, non-randomized phase 1/2 program. In phase 1, patients will receive fludarabine/cyclophosphamide lymphodepletion on Days -5 to -3, followed by three infusions of EB-DT-CAR-NK on Days 0, 3, and 7. A 3+3 dose-escalation structure with three planned dose levels will be used to determine dose-limiting toxicities, maximum tolerated dose, and/or recommended phase 2 dose.
In phase 2, patients will receive the recommended dose on the same schedule in an expansion cohort focused on CLDN18.2-positive gastric/GEJ adenocarcinoma, with prespecified subgroup analyses by HER2 status. The study will assess safety, objective response rate, disease control, durability, survival outcomes, and CAR-NK expansion/persistence. Correlative studies will explore the relationship between baseline CLDN18.2/HER2 expression and clinical outcome.
- Being tested
- EB-DT-CAR-NK, Fludarabine, Cyclophosphamide
- Keywords
- Solid tumor immunotherapy, Gastric cancer, GEJ cancer, Adoptive cellular immunotherapy, CAR-NK, Allogeneic NK cell therapy, CLDN18.2, HER2, ERBB2
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EB-DT-CAR-NKBiological
Allogeneic, cord-blood-derived CAR-NK cells engineered to target CLDN18.2 and HER2 (ERBB2). Planned phase 1 dose levels: 2 x 10^6, 4 x 10^6, and 8 x 10^6 cells/kg/infusion. Administered intravenously on Days 0, 3, and 7.
FludarabineDrug
Also called FC lymphodepletion regimen
Lymphodepleting chemotherapy administered intravenously at 30 mg/m^2/day on Days -5 to -3.
CyclophosphamideDrug
Also called FC lymphodepletion regimen
Lymphodepleting chemotherapy administered intravenously at 500 mg/m^2/day on Days -5 to -3.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Cohort | Experimental | Participants receive fludarabine and cyclophosphamide lymphodepletion on Days -5 to -3, followed by EB-DT-CAR-NK infusions on Days 0, 3, and 7. Three planned dose levels are explored using a 3+3 design. Receives: Biological: EB-DT-CAR-NK; Drug: Fludarabine; Drug: Cyclophosphamide |
| Dose Expansion Cohort | Experimental | Participants receive the recommended phase 2 dose (RP2D) on the same lymphodepletion and infusion schedule. Expansion is centered on CLDN18.2-positive gastric/GEJ adenocarcinoma, with HER2 status captured for exploratory subgroup analysis. Receives: Biological: EB-DT-CAR-NK; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs)
DLTs graded by CTCAE v5.0, with CRS and ICANS graded using ASTCT criteria.
Measured: 28 days
Determination of MTD
Dose-escalation decision based on DLT frequency and overall tolerability across planned cohorts.
Measured: 6 months
Objective response rate (ORR)
Confirmed complete response plus partial response according to RECIST v1.1 in evaluable subjects in the expansion cohort.
Measured: 12 months
Secondary outcomes (2)
Progression-free survival (PFS)
Time from first infusion to disease progression or death from any cause.
Measured: 12 months
Overall survival (OS)
Time from first infusion to death from any cause.
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 posted24 Apr 2026
- Study start2 Mar 2026
- Primary completion14 Mar 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 Advanced Gastric AdenocarcinomaStudies 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
- Phase 1 will use a non-randomized 3+3 dose-escalation design with three planned dose levels of the dual-target CAR-NK product after fludarabine/cyclophosphamide lymphodepletion. Phase 2 will enroll an expansion cohort at the recommended phase 2 dose using the same schedule. Cohort progression is sequential: dose-escalation first, then dose-expansion. All patients receive active study treatment; there is no placebo or standard-of-care control arm in this planning draft.
- Masking
- None (open label)
- Enrolment
- 36 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
- NCT07551362
- Sponsor's protocol ID
- ESSEN-DUET-GEJ-117
- Acronym
- DUET-GEJ
- Status last verified
- Apr 2026
- First submitted
- 18 Apr 2026
- Last updated
- 24 Apr 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 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open-label, Multicenter Study of Allogeneic Dual-target CLDN18.2/HER2 (ERBB2) CAR-NK Cells After Fludarabine/Cyclophosphamide Lymphodepletion in
- ClinicalTrials.gov ID
- NCT07551362
- Acronym / sponsor ID
- DUET-GEJ / ESSEN-DUET-GEJ-117
- Keywords
- Solid tumor immunotherapy, Gastric cancer, GEJ cancer, Adoptive cellular immunotherapy, CAR-NK, Allogeneic NK cell therapy, CLDN18.2, HER2
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Beijing BiotechIndustry (pharma, biotech, devices)
- Study start
- 2 Mar 2026 (actual)
- Primary completion
- 14 Mar 2027 (estimated)
- Study completion
- 17 Mar 2028 (estimated)
- First posted
- 24 Apr 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 example planning study proposes a phase 1/2 evaluation of an allogeneic, cord-blood-derived dual-target CAR-NK product directed against CLDN18.2 and HER2 (ERBB2) in adults with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma after prior standard systemic therapy. CLDN18.2 is selected as the anchor antigen because it has the more disease-specific gastric/GEJ cell-therapy development footprint, while HER2 is retained as the complementary second antigen to address co-expressing or heterogeneous disease. Phase 1 uses a 3+3 dose-escalation design after fludarabine/cyclophosphamide lymphodepletion followed by three intravenous CAR-NK infusions on Days 0, 3, and 7. Phase 2 expansion evaluates the recommended phase 2 dose and preliminary antitumor activity
Detailed description
This draft is intentionally modeled on current CLDN18.2- and HER2-directed cell-therapy studies on ClinicalTrials.gov and related primary publications. The key strategic choice is that HER2 and ERBB2 are treated as the same target; therefore the meaningful dual-target construct in gastric/GEJ cancer is CLDN18.2 plus HER2. The study is designed as a biomarker-driven, non-randomized phase 1/2 program. In phase 1, patients will receive fludarabine/cyclophosphamide lymphodepletion on Days -5 to -3, followed by three infusions of EB-DT-CAR-NK on Days 0, 3, and 7. A 3+3 dose-escalation structure with three planned dose levels will be used to determine dose-limiting toxicities, maximum tolerated dose, and/or recommended phase 2 dose.
In phase 2, patients will receive the recommended dose on the same schedule in an expansion cohort focused on CLDN18.2-positive gastric/GEJ adenocarcinoma, with prespecified subgroup analyses by HER2 status. The study will assess safety, objective response rate, disease control, durability, survival outcomes, and CAR-NK expansion/persistence. Correlative studies will explore the relationship between baseline CLDN18.2/HER2 expression and clinical outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase 1 will use a non-randomized 3+3 dose-escalation design with three planned dose levels of the dual-target CAR-NK product after fludarabine/cyclophosphamide lymphodepletion. Phase 2 will enroll an expansion cohort at the recommended phase 2 dose using the same schedule. Cohort progression is sequential: dose-escalation first, then dose-expansion. All patients receive active study treatment; there is no placebo or standard-of-care control arm in this planning draft.
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Cohort | Experimental | Biological: EB-DT-CAR-NK, Drug: Fludarabine, Drug: CyclophosphamideParticipants receive fludarabine and cyclophosphamide lymphodepletion on Days -5 to -3, followed by EB-DT-CAR-NK infusions on Days 0, 3, and 7. Three planned dose levels are explored using a 3+3 design. |
| Dose Expansion Cohort | Experimental | Biological: EB-DT-CAR-NK, Drug: Fludarabine, Drug: CyclophosphamideParticipants receive the recommended phase 2 dose (RP2D) on the same lymphodepletion and infusion schedule. Expansion is centered on CLDN18.2-positive gastric/GEJ adenocarcinoma, with HER2 status captured for exploratory subgroup analysis. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Signed informed consent before any study-specific procedure.
- Age 18 to 75 years.
- Histologically confirmed unresectable locally advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
- Central confirmation of CLDN18.2-positive disease by immunohistochemistry, defined for this draft as membranous CLDN18.2 expression in at least 10% of tumor cells. HER2 testing is required for all subjects; HER2-positive disease is defined as IHC 3+ or IHC 2+/ISH+ using gastric/GEJ testing criteria.
- Disease progression after at least 2 prior systemic regimens for advanced disease, including a fluoropyrimidine and platinum agent unless contraindicated or not tolerated. If HER2-positive, prior HER2-directed therapy is expected unless unavailable, contraindicated, or not tolerated.
Key exclusion criteria (11 listed)
- Prior CLDN18.2-targeted or HER2-targeted genetically modified cell therapy (CAR-T, CAR-NK, TCR-T, or similar).
- Active or untreated central nervous system metastases or leptomeningeal disease.
- Active uncontrolled infection, including uncontrolled HBV, HCV, or HIV viremia.
- Active autoimmune disease requiring systemic immunosuppression.
- Clinically significant uncontrolled cardiovascular disease, including recent myocardial infarction, unstable angina, uncontrolled arrhythmia, or severe heart failure.
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-DT-CAR-NKAllogeneic, cord-blood-derived CAR-NK cells engineered to target CLDN18.2 and HER2 (ERBB2). Planned phase 1 dose levels: 2 x 10^6, 4 x 10^6, and 8 x 10^6 cells/kg/infusion. Administered intravenously on Days 0, 3, and 7. | Biological | Dose Escalation Cohort, Dose Expansion Cohort |
| FludarabineAlso: FC lymphodepletion regimenLymphodepleting chemotherapy administered intravenously at 30 mg/m^2/day on Days -5 to -3. | Drug | Dose Escalation Cohort, Dose Expansion Cohort |
| CyclophosphamideAlso: FC lymphodepletion regimenLymphodepleting chemotherapy administered intravenously at 500 mg/m^2/day on Days -5 to -3. | Drug | Dose Escalation Cohort, Dose Expansion Cohort |
Primary outcome
Incidence of dose-limiting toxicities (DLTs)
Time frame: 28 days
DLTs graded by CTCAE v5.0, with CRS and ICANS graded using ASTCT criteria.
Determination of MTD
Time frame: 6 months
Dose-escalation decision based on DLT frequency and overall tolerability across planned cohorts.
Objective response rate (ORR)
Time frame: 12 months
Confirmed complete response plus partial response according to RECIST v1.1 in evaluable subjects in the expansion cohort.
2 secondary outcomes
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 24 Apr 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 EB-DT-CAR-NK, Fludarabine and Cyclophosphamide in people with Advanced Gastric Adenocarcinoma and Advanced Gastroesophageal Junction Adenocarcinoma, 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 11 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 24 Apr 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 shan 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 24 Apr 2026.