Dual-target CAR-NK therapy for adults with recurrent or progressive glioblastoma and other high-grade gliomas

Is this trial a fit for you?

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 tests locoregional delivery of off-the-shelf allogeneic CAR-NK cells engineered to recognize two tumor antigens selected from IL13Rα2, EGFR/EGFRvIII, and B7-H3. Tumor tissue will be profiled by immunohistochemistry and molecular testing, and participants will be assigned to a biomarker-defined cohort receiving the dual-target construct best matched to their antigen profile. The investigational product includes a built-in safety switch and may include an IL-15 support module, with lymphodepleting cyclophosphamide and fludarabine given per protocol. Primary objectives focus on safety and feasibility with exploratory measures of anti-tumor activity guiding later decisions.

Why it matters

Who can join: the full rules

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

• Peking University Shenzhen Hospital
  Shenzhen, Guangdong, China Recruiting

Study contacts

• Study coordinator: shan S Lu, Phd
• Email: Seni-Lu@beijing-biotech.com
• Phone: +86 13076790030

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.