P134 CAR‑T Cell Therapy for Recurrent Glioblastoma

A Phase I/II Clinical Study to Evaluate the Safety and Efficacy of P134 Cells in the Treatment of Recurrent Glioblastoma

This study will try P134 CAR‑T cells that target CD44 and CD133 to see if they are safe and can help control tumors in adults with recurrent IDH‑wildtype glioblastoma.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Tasly Pharmaceutical Group Co., Ltd (Industry-sponsored)
• Drugs / interventions: bevacizumab, chemotherapy, radiation, methotrexate, cyclophosphamide, prednisone, CAR-T
• Locations: 1 site (Beijing)
• Trial ID: NCT07318818 on ClinicalTrials.gov

What this trial studies

This is an open‑label, single‑arm Phase 1/2 trial using dose‑escalation followed by a dose‑expansion cohort to study P134 CD44/CD133 dual‑targeting CAR‑T cells in adults with recurrent IDH‑wildtype glioblastoma. Eligible participants are 18–70 years old with histologically or molecularly confirmed grade 4 IDH‑wildtype glioblastoma and at least one measurable lesion ≤3 cm; prior radiotherapy and/or temozolomide/bevacizumab is required. Patients must be suitable for neurosurgical placement of a CSF access device (e.g., Ommaya reservoir) for cell delivery and CSF sampling. The trial's main goals are to define safety and tolerability, identify the maximum tolerated dose and recommended Phase 2 dose, and characterize CAR‑T cytokinetic profiles in cerebrospinal fluid, with tumor response monitored by RANO criteria.

Who should consider this trial

Good fit: Adults 18–70 with recurrent or progressive grade 4 IDH‑wildtype glioblastoma who have at least one measurable lesion ≤3 cm, prior standard therapies (radiation/temozolomide ± bevacizumab), and are suitable for neurosurgical implantation of a CSF access device are the intended participants, with Phase II expansion requiring tumor CD44 or CD133 expression by IHC (≥1%).

Not a fit: Patients with IDH‑mutant gliomas, lesions larger than allowed, those who cannot undergo neurosurgical implantation for CSF access, or those without required antigen expression (for the Phase II expansion) are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, this targeted CAR‑T approach could provide a new treatment option that helps control tumor growth or delay progression in some patients with recurrent glioblastoma.

How similar studies have performed: Previous CAR‑T cell studies in glioblastoma have been early‑phase with limited and variable clinical benefit, so this dual‑targeting CD44/CD133 approach is relatively novel and remains unproven.

Eligibility criteria

Inclusion Criteria:

1. Voluntary written informed consent.
2. 18-70 years of age (inclusive), male or female.
3. Recurrent or progressive glioblastoma, histopathologically or molecularly diagnosed consistent with grade 4 glioblastoma (IDH wild-type) (refer to WHO Classification of Central Nervous System Tumors, 5th Edition, 2021).
4. Positive CD44 or CD133 antigen expression in tumor tissue confirmed by IHC, defined as ≥1% of tumor cells showing positive CD44 or CD133 IHC staining, regardless of intensity (applicable only in Phase II dose expansion study).
5. At least one measurable lesion meeting RANO 2.0 criteria and having a radiographically assessed measurable lesion ≤ 3 cm in longest diameter
6. Patient has received prior radiation therapy and/or temozolomide/bevacizumab.
7. The investigator confirmed that the patient was suitable for craniotomy cerebrospinal fluid shunt and accessory (Ommaya reservoir) implantation.

Exclusion Criteria:

1. Highly allergic constitution or history of severe allergy, or allergy to related cell products
2. Receipt of biologic anti-tumor therapy (including monoclonal or bispecific antibody-targeted therapy, immune checkpoint inhibitor therapy, etc.) within 6 weeks prior to PBMC collection; receipt of radiotherapy or surgery within 4 weeks prior to PBMC collection (excluding placement of vascular access devices; a 1-week washout period is acceptable for diagnostic biopsy surgeries); receipt of chemotherapy, hormone therapy (excluding hormone replacement therapy), or non-specific immunomodulatory therapy (such as interleukins, interferons, thymosin, cyclophosphamide, methotrexate, tumor necrosis factor, etc.) within 2 weeks prior to PBMC collection; receipt of traditional Chinese medicine therapy with a clear anticancer indication within 1 week prior to PBMC collection.
3. The adverse reactions caused by previous anti-tumor treatment have not recovered to ≤ Grade 1 as evaluated by NCI CTCAE v6.0 (except alopecia, skin pigmentation, leukoplakia, etc. which are assessed as having no safety risk).
4. Tumor metastasis to the brainstem or spinal cord.
5. Suffering from other serious neurological diseases other than brain tumors, such as meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, amyotrophic lateral sclerosis, spinal muscular atrophy, nerve paralysis, uncontrolled epilepsy, etc.
6. Patients with primary immunodeficiency disease, autoimmune diseases requiring medication (such as Crohn 's disease, ulcerative colitis, rheumatoid arthritis, systemic lupus), or previous history of autoimmune diseases of the nervous system (such as multiple sclerosis, Parkinson' s disease).
7. Receiving or requiring long-term use of immunosuppressive agents (except for physiological doses of systemic corticosteroids ≤ 10 mg/day prednisone equivalent, short-term ≤ 7 days corticosteroids for allergies, or topical glucocorticoids).
8. Trial participants who have a previous history of allogeneic bone marrow transplantation or organ transplantation, or are awaiting organ transplantation.
9. HBsAg positive and HBV DNA positive, HCV Ab positive and HCV RNA positive; Treponema pallidum antibody positive; human immunodeficiency virus (HIV) antibody positive.
10. Prior receipt of any gene therapy or cell therapy trial participant.
11. Pregnant or lactating women.
12. History of malignancy other than glioma within 5 years (except for adequately treated carcinoma in situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized prostate cancer, or stage I cervical cancer, which in the opinion of the investigator carries a minimal risk of recurrence).

Where this trial is running

Beijing

• Beijing Tiantan Hospital, Capital Medical University — Beijing, China (Recruiting)

Study contacts

• Principal investigator: Zhang Wei, Prof. — Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R.China
• Study coordinator: Zhang Yuping

Conditions Recurrent Glioblastoma IDH Wildtype