IL13Rα2 CAR-T for Patients With r/r Glioma (ENHANCING)

Safety, Tolerability and Efficacy of Enhanced IL-13Rα2 Targeted Chimeric Antigen Receptor T Cell Immunotherapy Against Recurrent/Refractory Grade 4 Glioma

This is a dose exploration clinical trial to assess the safety and feasibility of the IL13Ra2-targeted CAR-T in glioma.

Study Overview

• Status: Suspended
• Conditions: Glioma
• Intervention / Treatment: Biological: IL13Rα2 CAR-T

Detailed Description

Interleukin 13 receptor subunit alpha-2 (IL13Ra2A) is a high-affinity membrane receptor of the anti-inflammatory Th2 cytokine IL13, which is overexpressed in glioma and correlated with poor prognosis.

Chimeric antigen receptor (CAR) T cell therapy is a promising treatment approach for many malignancies. IL13Ra2-targeted CAR-T cells are under investigation in several clinical trials in primary CNS malignancies.

The investigators now designed a new structure CAR targeted IL13Ra2, and initiated a single arm, open, dose exploration clinical trial to evaluate the safety, tolerability, clinical efficacy, and pharmacokinetic characteristics of IL13Rα2 CAR-T for patients with glioma. This clinical trial will enroll 12-30 cases of patients with IL13α2-positive recurrent or refractory WHO grade 4 glioma (r/r WHO4 glioma), aiming to find the maximum tolerable dose (MTD), the recommended phase 2 dose (RP2D) and preliminary efficacy of the new structure IL13Ra2 CAR-T.

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

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Tiantan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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. Karnofsky scale score (KPS)≥50.
3. Subjects with WHO grade 4 gliomas who have relapsed or progressed during or after standard treatments such as surgery, radiotherapy, and chemotherapy.
4. Tumor with IL13Rα2 positive expression.
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 prior to the infusion of CAR-T cells, 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. Autoimmune diseases.
7. Severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes.
8. Subjects who have previously received cell therapy (such as TCR-T, CAR-T, TIL, etc.).
9. 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: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IL13Rα2 CAR-T; Biological: IL13Rα2 CAR-T	Biological: IL13Rα2 CAR-T; The IL13Rα2 CAR-T cells will be administered via intraventricular infusion every 2 weekly via an Ommaya reservoir.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of IL13Rα2 CAR-T	The safety of IL13Rα2 CAR-T will be assessed based on the totality of dose-limiting toxicity (DLT) and adverse event (AE) data collected during this phase.	Day 0 - Day 730

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	To evaluate the percentage of subjects who have a confirmed partial response (PR) and complete response (CR) per immunotherapy response assessment in neuro-oncology (iRANO) criteria.	Day 0 - Day 730
Duration of Response (DOR)	To evaluate the duration from the time that criteria are met for CR or PR per iRANO until disease progression or death due to any cause.	Day 0 - Day 730
Progression Free Survival (PFS)	To evaluate the time from the date of the first CAR-T infusion until disease progression per iRANO or death due to any cause.	Day 0 - Day 730
Overall Survival (OS)	To evaluate the time from the date of the first CAR-T infusion to death due to any cause.	Day 0 - Day 730
Overall Survival (OS) at 6 months (OS6)	To evaluate the percentage of survival subjects at 6 months after the first CAR-T infusion.	Day 0 - Day 180
Overall Survival (OS) at 12 months (OS12)	To evaluate the percentage of survival subjects at 12 months after the first CAR-T infusion.	Day 0 - Day 365
The levels of IL13Rα2 CAR-T cell and IL13Rα2 CAR in the CSF and peripheral blood	To detect the levels of IL13Rα2 CAR-T cell and IL13Rα2 CAR in the CSF and peripheral blood.	Day 0 - Day 730
The levels of cytokines in the CSF and peripheral blood	To detect levels of cytokines in the CSF and peripheral blood, cytokines will include IL-2, IL-6, IFN-γ, TNF-α, etc.	Day 0 - Day 730

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Exploratory Indicators	To analyze tumor microenvironment and CAR-T cell infiltrative levels in tumor tissues before and after treatment by immunohistochemistry and/or transcriptome sequencing, and explore the tumor or immune cell markers related to disease prognosis and IL13Rα2 expression.	Day 0 - Day 730

Collaborators and Investigators

• Sponsor: Yang Zhang
• Collaborators: TCRCure Biopharma Ltd.
• Investigators: Principal Investigator: Nan Ji, MD, PhD, Beijing Tiantan Hospital; Principal Investigator: Yang Zhang, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: March 23, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: r/r WHO4 glioma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: TT002

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