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Recruiting Phase 1

Dual-Targeting CAR-NK Cells for Recurrent/Progressive Glioblastoma and High-Grade Glioma

NCT07480941 · tracked via the Priya Life Science China tracker
Phase
Phase 1
Started
2026-02-02
Last updated
2026-03-18

Condition(s) studied

GlioblastomaHigh-grade GliomaMalignant GliomaRecurrent GlioblastomaRecurrent High-grade Glioma

Investigational drug(s) / intervention(s)

Dual-target CAR-NK cellsCyclophosphamide →Fludarabine →Intracranial catheter/reservoir for locoregional delivery

Dual-target CAR-NK cells: Dual-target CAR-NK cells

Cyclophosphamide: Cyclophosphamide

Fludarabine: Fludarabine

Intracranial catheter/reservoir for locoregional delivery: Intracranial catheter/reservoir for locoregional delivery

Study 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

Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
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.

Primary outcome measure(s)

  • Incidence of dose-limiting toxicities (DLTs) — 28 Days
    Incidence of dose-limiting toxicities (DLTs) after CAR-NK infusion (CTCAE v5.0; CRS and ICANS grading).
  • Maximum tolerated dose (MTD) — 12 months

Trial sites (1)

FacilityCityRegionStatus
Peking University Shenzhen Hospital Shenzhen Guangdong Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07480941 on ClinicalTrials.gov ↗ ← All trials in China