Dual-Targeting CAR-NK Cells for Recurrent/Progressive 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
Beijing Biotech
36 participants
Feb 2, 2026
INTERVENTIONAL
Conditions
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). 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.
Eligibility
Inclusion Criteria9
- 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 Criteria10
- 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.
Interventions
Dual-target CAR-NK cells
Cyclophosphamide
Fludarabine
Intracranial catheter/reservoir for locoregional delivery
Locations(1)
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NCT07480941