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
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.
• 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.