Dual-target CAR-NK cell therapy for recurrent glioblastoma and high-grade glioma
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 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 |
| Enrollment | 36 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Beijing Biotech Industry-sponsored |
| Drugs / interventions | CAR-T, chimeric antigen receptor, immunotherapy |
| Locations | 1 site (Shenzhen, Guangdong) |
| Trial ID | NCT07480941 on ClinicalTrials.gov |
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.
Who should consider this trial
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.
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.
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 performed: 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.
Eligibility criteria
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 this trial is running
Shenzhen, Guangdong
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.