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

NCT07480941 | Recruiting Phase 1 DMC

• 1 other identifier: EBNK-GBM-001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioblastoma; High-grade Glioma; Malignant Glioma; Recurrent Glioblastoma; Recurrent High-grade Glioma

Keywords

CAR-NK; dual targeting; IL13Rα2; EGFR; EGFRvIII; B7-H3; CD276; locoregional; intracavitary; Ommaya reservoir; biomarker-guided

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLTs)

  Incidence of dose-limiting toxicities (DLTs) after CAR-NK infusion (CTCAE v5.0; CRS and ICANS grading).

  28 Days

• Maximum tolerated dose (MTD)

  12 months

Secondary Outcomes (4)

• Objective response rate (ORR)

  12 months

• Disease control rate (DCR)

  6 months

• Progression-free survival (PFS)

  24 months

• Overall survival (OS)

  24 month

Study Arms (3)

IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK

EXPERIMENTAL

Participants whose tumors meet eligibility thresholds for IL13Rα2 and EGFR (and/or EGFRvIII) will receive a dual-target (tandem) CAR-NK product recognizing IL13Rα2 and EGFR/EGFRvIII.

Biological: Dual-target CAR-NK cells; Drug: Cyclophosphamide; Drug: Fludarabine; Device: Intracranial catheter/reservoir for locoregional delivery

IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK

EXPERIMENTAL

Participants whose tumors meet eligibility thresholds for IL13Rα2 and B7-H3 (CD276) will receive a dual-target (tandem) CAR-NK product recognizing IL13Rα2 and B7-H3.

Biological: Dual-target CAR-NK cells; Drug: Cyclophosphamide; Drug: Fludarabine; Device: Intracranial catheter/reservoir for locoregional delivery

EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK

EXPERIMENTAL

Participants whose tumors meet eligibility thresholds for EGFR (and/or EGFRvIII) and B7-H3 (CD276) will receive a dual-target (tandem) CAR-NK product recognizing EGFR/EGFRvIII and B7-H3.

Biological: Dual-target CAR-NK cells; Drug: Cyclophosphamide; Drug: Fludarabine; Device: Intracranial catheter/reservoir for locoregional delivery

Interventions

Fludarabine DRUG

Fludarabine

EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK; IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK; IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK

Intracranial catheter/reservoir for locoregional delivery DEVICE

Intracranial catheter/reservoir for locoregional delivery

EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK; IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK; IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK

Dual-target CAR-NK cells BIOLOGICAL

Dual-target CAR-NK cells

EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK; IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK; IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK

Cyclophosphamide DRUG

Cyclophosphamide

EGFR/EGFRvIII + B7-H3 (CD276) Dual-Target CAR-NK; IL13Rα2 + B7-H3 (CD276) Dual-Target CAR-NK; IL13Rα2 + EGFR/EGFRvIII Dual-Target CAR-NK

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open-label; participants and investigators are not masked.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Biomarker-guided, multi-cohort (umbrella) design. Participants are assigned to one of three cohorts based on tumor antigen expression, then treated in a cohort-specific modified 3+3 dose escalation followed by dose expansion at the recommended phase 2 dose (RP2D).

Study Record Dates

• First Submitted: March 14, 2026
• First Posted: March 18, 2026
• Study Start: February 2, 2026
• Primary Completion (Estimated): February 18, 2027
• Study Completion (Estimated): March 17, 2028
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

CN (1)