Dual-target CAR-NK therapy for adults with recurrent or progressive glioblastoma and other high-grade gliomas
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 study will try giving dual-target CAR-NK cells into the surgical cavity to see if they can help adults with recurrent or progressive glioblastoma or other high-grade gliomas.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 36 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Beijing Biotech Industry-sponsored |
| Drugs / interventions | CAR-T, chimeric antigen receptor, immunotherapy |
| Locations | 1 site (Shenzhen, Guangdong) |
| Trial ID | NCT07551336 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Ideal candidates are adults (18–75) with recurrent or progressive glioblastoma or other high-grade glioma, KPS ≥ 60, adequate organ function, and tumor tissue showing expression of at least two of IL13Rα2, EGFR/EGFRvIII, or B7-H3.
Not a fit: Patients whose tumors do not express at least two of the target antigens, who have poor performance status, significant organ dysfunction, or who cannot undergo the required surgical biopsy/resection and locoregional catheter placement are unlikely to benefit.
Why it matters
Potential benefit: If successful, this approach could provide a targeted immunotherapy that reduces tumor recurrence by attacking two antigens and lowering the chance of antigen-loss escape.
How similar studies have performed: Dual-target CAR-NK for high-grade glioma is largely novel, while prior single-target CAR-T/NK approaches have shown safety and occasional responses but limited durable benefit in early-phase studies.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
Shenzhen, Guangdong
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.