Actively Recruiting
Phase 1 Study of Locoregional Dual-Targeting CAR-NK Cells Against IL13Rα2, EGFR/EGFRvIII, and B7-H3 in Adults With Recurrent or Progressive Glioblastoma or High-Grade Glioma
Led by Beijing Biotech · Updated on 2026-04-24
36
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a first-in-human phase 1 study to assess a new treatment using dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells for adults with recurrent or progressive glioblastoma (GBM) or other high-grade gliomas (HGG). The study aims to reduce tumor escape by targeting two tumor-associated antigens selected from IL13Rα2, EGFR/EGFRvIII, and B7-H3 (CD276). Participants undergo tumor antigen profiling to determine the most suitable dual-target CAR construct based on their tumor's antigen expression. The investigational CAR-NK cells are off-the-shelf allogeneic natural killer cells genetically modified to express a tandem dual-target CAR. They are delivered directly to the tumor site via a catheter or reservoir placed during neurosurgery, targeting the surgical cavity wall or ventricular system to maximize local exposure while minimizing systemic effects. Dose escalation follows a modified 3+3 schema with up to three dose levels, followed by an expansion phase to further evaluate safety and possible repeated infusions at the recommended dose. Lymphodepleting chemotherapy with cyclophosphamide and fludarabine is given prior to CAR-NK infusion. Participants will have tumor response monitored by MRI using RANO criteria and be closely followed for adverse events including cytokine release syndrome and neurotoxicity. Tumor antigen testing involves immunohistochemistry and molecular methods using fresh or archived tumor tissue. Long-term safety follow-up will continue according to gene-modified cell therapy guidelines. The study includes assessments of dose-limiting toxicities during the first 28 days and determination of recommended phase 2 dose over 12 months. Total participation may last up to or beyond one year with regular safety and response evaluations.
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)
- Planned tumor resection or stereotactic biopsy, or availability of adequate archived tumor tissue for antigen testing
- Tumor expresses at least two of these antigens above set thresholds: IL13Rα2, EGFR (wild-type) and/or EGFRvIII, B7-H3 (CD276)
- Karnofsky Performance Status (KPS) of 60 or higher
- Adequate organ function as defined by laboratory tests
- Ability to undergo brain MRI with contrast unless contraindicated
- Negative pregnancy test for women of childbearing potential and agreement to use effective contraception during study and for a defined period after infusion
- Ability to understand and sign informed consent
You will not qualify if you...
- Active, uncontrolled infections including bacterial, viral, or fungal
- Known HIV infection with uncontrolled viral load; active hepatitis B or C with detectable viral load unless permitted
- Clinically significant autoimmune disease needing systemic immunosuppression within past 6 months
- Need for high-dose systemic corticosteroids (>4 mg/day dexamethasone equivalent) within 7 days before lymphodepletion or infusion
- Prior gene-modified cellular therapy within 6 months or prior therapy targeting IL13Rα2, EGFR/EGFRvIII, or B7-H3 that could affect safety assessment
- Diffuse leptomeningeal disease only or unsafe anatomy for catheter placement unless allowed
- Uncontrolled seizures despite optimal treatment
- Significant cardiovascular disease increasing risk for lymphodepletion or infusion
- Pregnant 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 - First 28 days with initial infusion and dose-limiting toxicity assessment; additional infusions possible during expansion stage up to 12 months
Participants receive lymphodepleting chemotherapy followed by locoregional infusions of dual-target CAR-NK cells administered via a neurosurgically placed catheter or reservoir, targeting tumor-associated antigens to treat recurrent or progressive glioblastoma or high-grade glioma.
Multiple visits during first 28 days for infusion and monitoring; follow-up visits scheduled during expansion stage over several months
Duration - Up to 12 months or longer per protocol
Participants are monitored for adverse events including cytokine release syndrome and neurotoxicity, with tumor response assessed by MRI at regular intervals and long-term safety follow-up for gene-modified cell therapy.
Regular MRI visits and safety monitoring visits during follow-up period
Trial Site Locations
Total: 1 location
1
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China, 518036
Actively Recruiting
Research Team
S
shan 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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