Actively Recruiting
A Phase 1 Study of Locoregional Dual-Targeting CAR-NK Cells Against IL13Rα2, EGFR/EGFRvIII, and/or B7-H3 in Adults With Recurrent or Progressive Glioblastoma or High-Grade Glioma
Led by Beijing Biotech · Updated on 2026-03-18
36
Participants Needed
1
Research Sites
56 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a first-in-human Phase 1 study to test dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells delivered locally for adults with recurrent or progressive glioblastoma or other high-grade gliomas. The study aims to address tumor heterogeneity by using CAR-NK cells that recognize two tumor antigens selected from IL13Rα2, EGFR/EGFRvIII, and B7-H3 (CD276) to reduce the risk of antigen escape. Participants undergo tumor antigen profiling to determine the most suitable dual-target CAR construct for their tumor. The investigational CAR-NK cells are off-the-shelf allogeneic cells genetically modified to express dual-target CARs with a built-in safety switch and potentially an NK-support cytokine module for persistence. These cells are administered locoregionally through a neurosurgically placed catheter or reservoir into the surgical cavity wall or ventricular system to maximize tumor exposure while limiting systemic effects. The study follows a dose-escalation design with up to three dose levels per biomarker-defined cohort, followed by an expansion phase to further assess safety and preliminary activity. Participants may receive repeat infusions at the recommended dose. Tumor antigen profiles categorize participants into one of three groups receiving CAR-NK cells targeting the two highest-priority tumor antigens. Participants will have tumor tissue tested by immunohistochemistry and molecular methods to guide treatment assignment. They will be closely monitored for adverse events including cytokine release syndrome and neurotoxicity. Tumor response will be assessed by MRI using RANO criteria at regular intervals. Safety and activity will be evaluated during the first 28 days and up to 12 months after infusion. Long-term follow-up for gene-modified cell therapy safety will be conducted per guidelines. The total study duration includes active treatment, dose escalation, expansion, and extended monitoring periods.
CONDITIONS
Brief Title
Dual-Targeting CAR-NK Cells for Recurrent/Progressive Glioblastoma and High-Grade Glioma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 to 75 years at the time of consent
- Histologically confirmed recurrent or progressive glioblastoma (WHO grade 4) or diffuse high-grade glioma (WHO grade 3 or 4) after standard therapy
- Planned tumor resection or stereotactic biopsy, or availability of adequate archived tumor tissue for antigen testing and catheter placement
- Tumor expresses at least two of the following above protocol thresholds: IL13Rα2, EGFR (wild-type) and/or EGFRvIII, B7-H3 (CD276)
- Karnofsky Performance Status of 60 or higher
- Adequate hematologic, renal, and hepatic organ function per protocol
- Ability to undergo brain MRI with contrast unless contraindicated
- Negative pregnancy test for women of childbearing potential and agreement to use effective contraception during and after the study
- Ability to understand and sign informed consent
You will not qualify if you...
- Active, uncontrolled infection including bacterial, viral, or fungal infections
- Known HIV infection with uncontrolled viral load; active hepatitis B or C with detectable viral load unless permitted
- Clinically significant autoimmune disease requiring systemic immunosuppression within past 6 months
- Requirement for high-dose systemic corticosteroids (>4 mg/day dexamethasone equivalent) within 7 days before lymphodepletion or infusion, except physiologic replacement
- Prior gene-modified cellular therapy within 6 months or prior therapy targeting IL13Rα2, EGFR/EGFRvIII, or B7-H3 that may confound safety
- Diffuse leptomeningeal disease only or anatomy preventing safe catheter placement unless allowed
- Uncontrolled seizures despite optimal medical therapy
- Clinically significant cardiovascular disease increasing risk of treatment procedures
- Pregnancy or breastfeeding
- Any condition making participation unsuitable or interfering with protocol adherence
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 screening and enrollment visit
Duration - Several days prior to treatment infusion
Participants undergo lymphodepletion chemotherapy with cyclophosphamide and fludarabine prior to receiving the investigational treatment.
1 to 2 visits for chemotherapy administration
Duration - Dose escalation phase includes 28 days after first infusion; expansion phase may include repeated infusions at recommended dose
Participants receive locoregional infusions of dual-target CAR-NK cells via a neurosurgically placed intracranial catheter/reservoir.
Multiple visits including infusion day and weekly monitoring visits for up to 28 days and possible additional visits during expansion
Duration - Up to 24 months after treatment
Participants are monitored for adverse events, tumor response via MRI, and long-term safety of gene-modified cell therapy.
Regular MRI assessments and clinical monitoring visits at scheduled intervals
Trial Site Locations
Total: 1 location
1
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China, 518036
Actively Recruiting
Research Team
S
Seni S Lu, Phd
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
3
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