Safety and Efficacy Study of Anti-B7-H3 CAR-T Cell Therapy for Recurrent Glioblastoma

An Open, Single-arm, Phase 1 Study to Evaluate the Safety/Preliminary Effectiveness and Determine the Maximal Tolerated Dose of B7-H3-targeting CAR-T Cell Therapy in Treating Recurrent Glioblastomas

This is an open, single-arm, dose-escalation and multiple-dose study to evaluate the safety, tolerability and preliminary effectiveness of B7-H3-targeting Chimeric Antigen Receptor-T (CAR-T) cell therapy on patients with recurrent glioblastomas. The study also plan to explore the Maximum Tolerated Dose (MTD) and determine the Recommended Phase II Dose (RP2D) of the CAR-T cell therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Biological: B7-H3-targeting CAR-T cells

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Beijing Tiantan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, aged 18-75 years (including 18 and 75 years old)；
2. Patients with relapsed glioblastoma, as confirmed by positron emission tomography (PET) or histologic pathology；
3. A >= 30% staining extent of B7-H3 in his/her primary/recurrent tumor tissue by the immunochemical method;
4. Karnofsky scale score>=50
5. Availability in collecting peripheral blood mononuclear cells (PBMCs) ；
6. Adequate laboratory values and adequate organ function;
7. Patients with childbearing/fathering potential must agree to use highly effective contraception；

Exclusion Criteria:

1. Pregnant or breastfeeding females；
2. Contraindication to bevacizumab；
3. Within 5 days before the CAR-T cell infusion, subjects receiving systemic administration of steroids with dosage more than 10mg/d prednisone or the equivalent doses of other steroids ( not including inhaled corticosteroid)；
4. Comorbid with Other uncontrolled malignancy；
5. Active immunodeficiency virus (HIV) or hepatitis B virus or hepatitis C virus or tuberculosis infection;
6. Subjects receiving the placement of a carmustine slow-release wafer within 6 months before the enrollment;
7. Autoimmune diseases;
8. Receiving long-term immunosuppressive treatment after organ transplantation;
9. Severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes;
10. Not recovered from the toxicities or side effects by previous treatment;
11. Subjects who have participated the other interventional trial within one month before the enrollment, or have received other CAR-T cell therapies or gene-modified cell therapy before enrollment.
12. Subjects with medical conditions that affect signing the written informed consent or complying with the research procedures, the medical conditions including, but not limited to cardio-cerebral vascular diseases, renal dysfunction/failure, pulmonary embolism, coagulation disorders, active systemic infection, uncontrolled infection et. al; or patients who are unwilling or unable to comply with the research procedures; these
13. Subjects with other conditions that would interfere trial participation at the investigator's discretion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CAR-T cell therapy; Dose-escalation phase: A "3+3" dose-escalation design is used to determine MTD & R2PD. Anti-B7-H3 autologous CAR-T cells were given biweekly to patients at the following doses for each cycle, and 4 cycles as one course. Dose1: 3 patients at a dose of 20 million cells for each cycle. Dose 2: 3 patients at a dose of 60 million cells for each cycle. Dose 3: 3 patients at a dose of 150 million cells for each cycle. Dose 4: 3 patients at a dose of 450 million cells for each cycle. Dose 5: 3 patients at a dose of 900 million cells for each cycle. R2PD confirmation phase: Determine the R2PD based on the results from the previous dose-escalation study; Treat another 12 patients with anti-B7-H3 autologous CAR-T cells biweekly at the R2PD to further confirm the safety of R2PD. At each dose phase, if the patients show tolerate and response to the treatment, these patients would receive several courses of treatment at PI's discretion.

Biological: B7-H3-targeting CAR-T cells; Patients will be treated with anti-B7-H3 autologous CAR-T cells that are delivered into the intracranial tumor resection cavity or ventricular system using an Ommaya device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting Toxicity (DLT)	To evaluate the DLT incidence occurred within three months after B7-H3 CAR-T cells infusion	three months post CAR-T cells infusion
Safety：Incidence and severity of adverse events	To evaluate the possible adverse events occurred within three months after B7-H3 CAR-T cell infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity	three months post CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy：Overall survival rate at 12 months	The proportion of subjects who have survived for more than 12 months since the diagnosis of recurrent glioblastoma	12 months post CAR-T cells infusion
Efficacy：objective remission rate	The proportion of subjects reaching complete remission / partial remission in optimal remission	1, 2, 3, 4, 5, 6 months post CAR-T cells infusion
pharmacokinetics：Cmax	observed maximum plasma concentration (Cmax)	Samples collected pre-injection, and 1, 2, 3, 5, 7, 9, 11,13 days post the first injection; Samples collected pre-injection, and 2, 7, 13 days post re-injections
pharmacokinetics：Tmax	time to reach maximum plasma concentration (tmax)	Samples collected pre-injection, and 1, 2, 3, 5, 7, 9, 11,13 days post the first injection; Samples collected pre-injection, and 2, 7, 13 days post re-injections
pharmacokinetics：AUC	area under the plasma concentration-time curve from time zero to 28 days after dosing (AUC(0-28))	Sample taken pre-injection, and 1, 2, 3, 5, 7, 9, 11,13 days post the first injection; Sample taken pre-injection, and 2,7,13 days post re-injections

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Nan Ji, Dr., Beijing Tiantan Hospital

Publications and helpful links

General Publications

• Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121.

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2022
• Primary Completion (Actual): November 30, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: February 11, 2022
• First Posted (Actual): February 15, 2022

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: TX103T-IG005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No