GlioblastomaPhase 1DUAL-CAR-NK-GBNCT07480941
Dual-Targeting CAR-NK Cells for Recurrent/Progressive Glioblastoma and High-Grade Glioma
A Phase 1 study testing Dual-target CAR-NK cells, Cyclophosphamide and Fludarabine in people with Glioblastoma and High-grade Glioma, run by Beijing Biotech at 1 site in China.
Trial summary
This is a draft, ClinicalTrials.gov-style example record for a first-in-human Phase 1 study evaluating locoregional administration of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in adults with recurrent or progressive glioblastoma (GBM) or other high-grade glioma (HGG). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Glioblastoma, High-grade Glioma, Malignant Glioma
- What is being tested?
- Dual-target CAR-NK cells, Cyclophosphamide and Fludarabine
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 2 Feb 2026to 17 Mar 2028
- Phase
- Phase 1
- 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
- Age 18 to 75 years at the time of consent.
- Histologically confirmed glioblastoma (WHO grade 4) or diffuse high-grade glioma (WHO grade 3 or 4) that is recurrent or progressive after standard therapy.
- Planned clinically indicated tumor resection or stereotactic biopsy (or availability of adequate archived tumor tissue) to support antigen testing and locoregional catheter placement.
- Tumor demonstrates expression of at least two of the following antigens above protocol-defined thresholds: IL13Rα2, EGFR (wild-type) and/or EGFRvIII, B7-H3 (CD276).
- Karnofsky Performance Status (KPS) ≥ 60.
- Adequate organ function (hematologic, renal, hepatic) as defined by protocol laboratory criteria.
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- Ability to undergo brain MRI with contrast (unless contraindicated and alternative imaging is permitted).
- Negative pregnancy test for women of childbearing potential; agreement to use effective contraception during study participation and for a protocol-defined period after infusion.
- Ability to understand and willingness to sign informed consent.
Who cannot join
- Active, uncontrolled infection (including uncontrolled bacterial, viral, or fungal infection).
- Known HIV infection with uncontrolled viral load; active hepatitis B or hepatitis C with detectable viral load (unless permitted per protocol).
- Clinically significant autoimmune disease requiring systemic immunosuppression within the past 6 months.
- Requirement for high-dose systemic corticosteroids (e.g., >4 mg/day dexamethasone equivalent) within 7 days prior to lymphodepletion/infusion (physiologic replacement permitted).
- Prior gene-modified cellular therapy (e.g., prior CAR-T/CAR-NK) within 6 months, or prior therapy targeting IL13Rα2, EGFR/EGFRvIII, or B7-H3 where residual engineered cells could confound safety assessments.
- Diffuse leptomeningeal disease as the only site of disease, or anatomy that precludes safe catheter placement (unless specifically allowed by protocol).
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- Uncontrolled seizures despite optimal medical therapy.
- Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia) that would increase risk with lymphodepletion or infusion procedures.
- Pregnant or breastfeeding.
- Any condition that, in the investigator's judgment, would make the participant unsuitable for the study or could interfere with protocol adherence.
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, First-in-Human, Biomarker-Guided, Dose-Escalation and Expansion Study of Locoregional Dual-Targeting CAR-NK Cells Directed Against IL13Rα2, EGFR/EGFRvIII, and/or B7-H3 (CD276) in Adults With Recurrent or Progressive Glioblastoma or High-Grade Glioma
This is a draft, ClinicalTrials.gov-style example record for a first-in-human Phase 1 study evaluating locoregional administration of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in adults with recurrent or progressive glioblastoma (GBM) or other high-grade glioma (HGG). Participants will undergo tumor antigen profiling for IL13Rα2, EGFR/EGFRvIII, and B7-H3 (CD276). Based on this assessment, each participant will receive the most suitable dual-target CAR construct to reduce antigen-escape risk.
Read the detailed description
Rationale: GBM/HGG is molecularly heterogeneous and may evade single-antigen immunotherapy via antigen loss or heterogeneous antigen expression. This study evaluates a dual-target CAR-NK strategy that can recognize two tumor-associated antigens selected from IL13Rα2, EGFR/EGFRvIII, and B7-H3 (CD276). Target assessment and cohort assignment: At screening, archived and/or fresh tumor tissue (from clinically indicated resection or biopsy) will be evaluated by immunohistochemistry (IHC) for IL13Rα2, EGFR, and B7-H3, and by molecular testing (e.g., RT-PCR or NGS) for EGFRvIII when applicable. Participants will be assigned to one of three biomarker-defined cohorts based on the two highest-priority antigens detected above protocol-defined thresholds. An internal review committee may recommend prioritizing one construct for later expansion based on emerging safety/feasibility/activity signals. Investigational product: The investigational products are off-the-shelf allogeneic CAR-NK cells manufactured from a standardized NK-cell source (e.g., iPSC-derived NK cells or a qualified NK master cell bank) and genetically modified to express a tandem (dual-target) CAR. The constructs include a built-in safety switch (e.g., inducible caspase-9) and may include an NK-support cytokine module (e.g., IL-15) to enhance persistence. The exact dual-target construct used for each participant depends on the screening antigen profile.
Route of administration: CAR-NK cells will be delivered locoregionally to the surgical cavity wall and/or into the ventricular system via a neurosurgically placed catheter/reservoir, to maximize exposure at the tumor site while limiting systemic exposure. Dose escalation and expansion: Each biomarker-defined cohort follows a modified 3+3 dose-escalation schema with up to three dose levels (e.g., 1×10^7, 3×10^7, and 1×10^8 CAR-NK cells per infusion). Dose-limiting toxicities (DLTs) will be assessed during the first 28 days after the first infusion. After an RP2D is identified within a cohort, an expansion stage will further characterize safety and preliminary activity and may allow repeat infusions at the RP2D. Follow-up: Participants will be monitored closely for adverse events including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Tumor response will be assessed with MRI using RANO criteria at regular intervals. Long-term follow-up for gene-modified cell therapy safety will be conducted per applicable guidance.
- Conditions
- Glioblastoma, High-grade Glioma, Malignant Glioma, Recurrent Glioblastoma, Recurrent High-grade Glioma
- Being tested
- Dual-target CAR-NK cells, Cyclophosphamide, Fludarabine, Intracranial catheter/reservoir for locoregional delivery
- Keywords
- CAR-NK, dual targeting, IL13Rα2, EGFR, EGFRvIII, B7-H3, CD276, locoregional, intracavitary, Ommaya reservoir, biomarker-guided
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dual-target CAR-NK cellsBiological
Dual-target CAR-NK cells
CyclophosphamideDrug
Cyclophosphamide
FludarabineDrug
Fludarabine
Intracranial catheter/reservoir for locoregional deliveryDevice
Intracranial catheter/reservoir for locoregional delivery
| Study group | Role | What they receive |
|---|---|---|
| IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK | Experimental | Participants whose tumors meet eligibility thresholds for IL13Rα2 and EGFR (and/or EGFRvIII) will receive a dual-target (tandem) CAR-NK product recognizing IL13Rα2 and EGFR/EGFRvIII. Receives: Biological: Dual-target CAR-NK cells; Drug: Cyclophosphamide; Drug: Fludarabine; Device: Intracranial catheter/reservoir for locoregional delivery |
| IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK | Experimental | Participants whose tumors meet eligibility thresholds for IL13Rα2 and B7-H3 (CD276) will receive a dual-target (tandem) CAR-NK product recognizing IL13Rα2 and B7-H3. Receives: Biological: Dual-target CAR-NK cells; Drug: Cyclophosphamide; Drug: Fludarabine; Device: Intracranial catheter/reservoir for locoregional delivery |
| EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK | Experimental | Participants whose tumors meet eligibility thresholds for EGFR (and/or EGFRvIII) and B7-H3 (CD276) will receive a dual-target (tandem) CAR-NK product recognizing EGFR/EGFRvIII and B7-H3. Receives: Biological: Dual-target CAR-NK cells; Drug: Cyclophosphamide; Drug: Fludarabine; Device: Intracranial catheter/reservoir for locoregional delivery |
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) after CAR-NK infusion (CTCAE v5.0; CRS and ICANS grading).
Measured: 28 Days
Maximum tolerated dose (MTD)
Measured: 12 months
Secondary outcomes (4)
Objective response rate (ORR)
Objective response rate (ORR) by RANO criteria (CR+PR).
Measured: 12 months
Disease control rate (DCR)
Measured: 6 months
Progression-free survival (PFS)
Measured: 24 months
Overall survival (OS)
Measured: 24 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2026
- Study start2 Feb 2026
- Primary completion18 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 GlioblastomaStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Biomarker-guided, multi-cohort (umbrella) design. Participants are assigned to one of three cohorts based on tumor antigen expression, then treated in a cohort-specific modified 3+3 dose escalation followed by dose expansion at the recommended phase 2 dose (RP2D).
- 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
- NCT07480941
- Sponsor's protocol ID
- EBNK-GBM-001
- Acronym
- DUAL-CAR-NK-GB
- Status last verified
- Mar 2026
- First submitted
- 14 Mar 2026
- Last updated
- 18 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 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, First-in-Human, Biomarker-Guided, Dose-Escalation and Expansion Study of Locoregional Dual-Targeting CAR-NK Cells Directed Against IL13Rα2, EGFR/EGFRvIII, and/or B7-H3 (CD276) in Adults With Recurrent or Progressive Glioblastoma or High-Grade Glioma
- ClinicalTrials.gov ID
- NCT07480941
- Acronym / sponsor ID
- DUAL-CAR-NK-GB / EBNK-GBM-001
- Conditions
- Glioblastoma, High-grade Glioma, Malignant Glioma, Recurrent Glioblastoma, Recurrent High-grade Glioma
- Keywords
- CAR-NK, dual targeting, IL13Rα2, EGFR, EGFRvIII, B7-H3, CD276, locoregional
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Beijing BiotechIndustry (pharma, biotech, devices)
- Study start
- 2 Feb 2026 (actual)
- Primary completion
- 18 Feb 2027 (estimated)
- Study completion
- 17 Mar 2028 (estimated)
- First posted
- 18 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 draft, ClinicalTrials.gov-style example record for a first-in-human Phase 1 study evaluating locoregional administration of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in adults with recurrent or progressive glioblastoma (GBM) or other high-grade glioma (HGG). Participants will undergo tumor antigen profiling for IL13Rα2, EGFR/EGFRvIII, and B7-H3 (CD276). Based on this assessment, each participant will receive the most suitable dual-target CAR construct to reduce antigen-escape risk.
Detailed description
Rationale: GBM/HGG is molecularly heterogeneous and may evade single-antigen immunotherapy via antigen loss or heterogeneous antigen expression. This study evaluates a dual-target CAR-NK strategy that can recognize two tumor-associated antigens selected from IL13Rα2, EGFR/EGFRvIII, and B7-H3 (CD276). Target assessment and cohort assignment: At screening, archived and/or fresh tumor tissue (from clinically indicated resection or biopsy) will be evaluated by immunohistochemistry (IHC) for IL13Rα2, EGFR, and B7-H3, and by molecular testing (e.g., RT-PCR or NGS) for EGFRvIII when applicable. Participants will be assigned to one of three biomarker-defined cohorts based on the two highest-priority antigens detected above protocol-defined thresholds. An internal review committee may recommend prioritizing one construct for later expansion based on emerging safety/feasibility/activity signals. Investigational product: The investigational products are off-the-shelf allogeneic CAR-NK cells manufactured from a standardized NK-cell source (e.g., iPSC-derived NK cells or a qualified NK master cell bank) and genetically modified to express a tandem (dual-target) CAR. The constructs include a built-in safety switch (e.g., inducible caspase-9) and may include an NK-support cytokine module (e.g., IL-15) to enhance persistence. The exact dual-target construct used for each participant depends on the screening antigen profile.
Route of administration: CAR-NK cells will be delivered locoregionally to the surgical cavity wall and/or into the ventricular system via a neurosurgically placed catheter/reservoir, to maximize exposure at the tumor site while limiting systemic exposure. Dose escalation and expansion: Each biomarker-defined cohort follows a modified 3+3 dose-escalation schema with up to three dose levels (e.g., 1×10^7, 3×10^7, and 1×10^8 CAR-NK cells per infusion). Dose-limiting toxicities (DLTs) will be assessed during the first 28 days after the first infusion. After an RP2D is identified within a cohort, an expansion stage will further characterize safety and preliminary activity and may allow repeat infusions at the RP2D. Follow-up: Participants will be monitored closely for adverse events including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Tumor response will be assessed with MRI using RANO criteria at regular intervals. Long-term follow-up for gene-modified cell therapy safety will be conducted per applicable guidance.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Biomarker-guided, multi-cohort (umbrella) design. Participants are assigned to one of three cohorts based on tumor antigen expression, then treated in a cohort-specific modified 3+3 dose escalation followed by dose expansion at the recommended phase 2 dose (RP2D).
| Arm | Type | Receives |
|---|---|---|
| IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK | Experimental | Biological: Dual-target CAR-NK cells, Drug: Cyclophosphamide, Drug: Fludarabine, Device: Intracranial catheter/reservoir for locoregional deliveryParticipants whose tumors meet eligibility thresholds for IL13Rα2 and EGFR (and/or EGFRvIII) will receive a dual-target (tandem) CAR-NK product recognizing IL13Rα2 and EGFR/EGFRvIII. |
| IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK | Experimental | Biological: Dual-target CAR-NK cells, Drug: Cyclophosphamide, Drug: Fludarabine, Device: Intracranial catheter/reservoir for locoregional deliveryParticipants whose tumors meet eligibility thresholds for IL13Rα2 and B7-H3 (CD276) will receive a dual-target (tandem) CAR-NK product recognizing IL13Rα2 and B7-H3. |
| EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK | Experimental | Biological: Dual-target CAR-NK cells, Drug: Cyclophosphamide, Drug: Fludarabine, Device: Intracranial catheter/reservoir for locoregional deliveryParticipants whose tumors meet eligibility thresholds for EGFR (and/or EGFRvIII) and B7-H3 (CD276) will receive a dual-target (tandem) CAR-NK product recognizing EGFR/EGFRvIII and B7-H3. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18 to 75 years at the time of consent.
- Histologically confirmed glioblastoma (WHO grade 4) or diffuse high-grade glioma (WHO grade 3 or 4) that is recurrent or progressive after standard therapy.
- Planned clinically indicated tumor resection or stereotactic biopsy (or availability of adequate archived tumor tissue) to support antigen testing and locoregional catheter placement.
- Tumor demonstrates expression of at least two of the following antigens above protocol-defined thresholds: IL13Rα2, EGFR (wild-type) and/or EGFRvIII, B7-H3 (CD276).
- Karnofsky Performance Status (KPS) ≥ 60.
Key exclusion criteria (10 listed)
- Active, uncontrolled infection (including uncontrolled bacterial, viral, or fungal infection).
- Known HIV infection with uncontrolled viral load; active hepatitis B or hepatitis C with detectable viral load (unless permitted per protocol).
- Clinically significant autoimmune disease requiring systemic immunosuppression within the past 6 months.
- Requirement for high-dose systemic corticosteroids (e.g., >4 mg/day dexamethasone equivalent) within 7 days prior to lymphodepletion/infusion (physiologic replacement permitted).
- Prior gene-modified cellular therapy (e.g., prior CAR-T/CAR-NK) within 6 months, or prior therapy targeting IL13Rα2, EGFR/EGFRvIII, or B7-H3 where residual engineered cells could confound safety assessments.
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 cellsDual-target CAR-NK cells | Biological | EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK, IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK, IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK |
| CyclophosphamideCyclophosphamide | Drug | EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK, IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK, IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK |
| FludarabineFludarabine | Drug | EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK, IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK, IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK |
| Intracranial catheter/reservoir for locoregional deliveryIntracranial catheter/reservoir for locoregional delivery | Device | EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK, IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK, IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK |
Primary outcome
Incidence of dose-limiting toxicities (DLTs)
Time frame: 28 Days
Incidence of dose-limiting toxicities (DLTs) after CAR-NK infusion (CTCAE v5.0; CRS and ICANS grading).
Maximum tolerated dose (MTD)
Time frame: 12 months
4 secondary outcomes
Objective response rate (ORR)
Time frame: 12 months
Disease control rate (DCR)
Time frame: 6 months
Progression-free survival (PFS)
Time frame: 24 months
Overall survival (OS)
Time frame: 24 month
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 18 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 study testing Dual-target CAR-NK cells, Cyclophosphamide and Fludarabine in people with Glioblastoma and High-grade Glioma, 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 9 inclusion and 10 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 18 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 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.
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 18 Mar 2026.