Dual-target CAR-NK cell therapy for recurrent glioblastoma and high-grade glioma
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
Run by Beijing Biotech · NCT07480941 · Data updated 2026-11-12
This phase 1 study will test whether injecting dual-target CAR-NK cells into the brain is safe and can help adults with recurrent or progressive glioblastoma or other high-grade gliomas.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Enrollment | 36 (estimated) |
| Sponsor | Beijing Biotech Industry-sponsored |
| Drugs / interventions | CAR-T, chimeric antigen receptor, immunotherapy |
| Locations | 1 site (Shenzhen, Guangdong) |
| Status | Recruiting |
| Started | February 2, 2026 |
| Main results expected | February 18, 2027 |
| Study ends | March 17, 2028 |
| Registry record updated | March 18, 2026 |
| Trial ID | NCT07480941 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Adults 18–75 with histologically confirmed recurrent or progressive glioblastoma or other high-grade glioma whose tumors express at least two of IL13Rα2, EGFR/EGFRvIII, or B7-H3, with KPS ≥60 and ability to undergo resection/biopsy and intracranial catheter placement, are the intended candidates.
✕Probably not a fit
Patients whose tumors do not meet the dual-antigen expression thresholds, who cannot tolerate surgery or lymphodepleting chemotherapy, who have very poor performance status, or who are pregnant are unlikely to benefit from this protocol.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This first-in-human Phase 1 trial delivers off-the-shelf, allogeneic CAR-NK cells engineered to recognize two tumor antigens selected from IL13Rα2, EGFR/EGFRvIII, and B7-H3. Tumor tissue is profiled by immunohistochemistry and molecular testing to identify the two highest-priority antigens and assign each participant to the matching dual-target construct cohort. Participants undergo lymphodepletion with cyclophosphamide and fludarabine, placement of an intracranial catheter/reservoir for locoregional delivery, and one or more locoregional infusions of the selected CAR-NK product that includes a built-in safety switch and optional IL-15 support. Safety, feasibility, and early signals of anti-tumor activity will be monitored to guide dose escalation and any cohort expansion.
Why it matters
Potential benefit: If successful, this dual-target approach could lower the chance of antigen-loss relapse and provide more durable tumor control than single-antigen therapies, potentially delaying progression and extending survival.
How similar studies have gone: Single-antigen CAR-T and CAR-NK approaches for glioma have shown limited early signals but are frequently undermined by antigen escape, so the dual-target CAR-NK strategy is largely novel and unproven in humans.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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. * 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. Exclusion Criteria: * 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). * 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.
Where it's running
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Peking University Shenzhen Hospital
Shenzhen, Guangdong, China Recruiting
Study contacts
- Study coordinator: Seni S Lu, Phd
- Email: Seni-Lu@beijing-biotech.com
- Phone: +86 13076790030
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.