IL13Rα2 CAR-T Cells Secreting Anti-PD-L1 Antibody for Recurrent Malignant Glioma (APIC-RG)

A Multicenter, Open-Label, Non-Randomized, Single-Arm Investigator-Initiated Trial to Evaluate the Safety and Efficacy of IL13Rα2 CAR-T Cells Secreting Anti-PD-L1 Antibody in Patients With Recurrent Malignant Glioma

This clinical study is designed to evaluate the safety and efficacy of IL13Rα2 CAR-T cells secreting anti-PD-L1 antibody in patients with recurrent malignant glioma. This trial is a multicenter, open-label, non-randomized, single-arm investigator-initiated trial (IIT). Patients who have recurrent malignant glioma will receive IL13Rα2 CAR-T cell therapy and will be monitored for safety, adverse events (AEs), and efficacy outcomes, including overall survival (OS) and progression-free survival (PFS). The study will help assess the potential of this innovative therapy in the treatment of glioma and its ability to control tumor growth by targeting both IL13Rα2 and PD-L1.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent Malignant Glioma
• Intervention / Treatment: Biological: IL13Rα2 CAR-T Cells Secreting Anti-PD-L1 Antibody

Detailed Description

The primary aim of this study is to evaluate the safety and efficacy of IL13Rα2 CAR-T cells secreting anti-PD-L1 antibody for the treatment of recurrent malignant glioma. Malignant gliomas are aggressive brain tumors with limited treatment options and poor prognosis. Immunotherapy, including CAR-T cells, has shown promise in various cancers, but its application in glioma treatment remains under investigation.

This study will involve patients with recurrent glioma who have failed prior treatments. Participants will receive a single infusion of IL13Rα2 CAR-T cells, which are engineered to recognize and target tumor cells expressing IL13Rα2. The CAR-T cells will be combined with the secretion of anti-PD-L1 antibodies, aimed at overcoming the immune checkpoint inhibition in the tumor microenvironment.

Safety will be assessed by monitoring adverse events (AEs) and cytokine release syndrome (CRS). The efficacy will be evaluated by measuring tumor response, progression-free survival (PFS), and overall survival (OS) over a follow-up period of several months. The study will also assess changes in the immune microenvironment, including immune cell infiltration and expression of immune checkpoint markers.

The trial will be conducted across multiple centers, including major hospitals in China. It aims to provide valuable data on the potential of this dual-target CAR-T therapy in treating gliomas and to assess its feasibility as a clinical treatment option.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ming Yang, Medical Doctor; Phone Number: +86 138 1065 5237; Email: yangming@cicams.ac.cn

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
      • Contact: Hongliang Mao, Medical Doctor; Phone Number: +86 18756909374; Email: Mao.HL@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Recurrent malignant glioma (WHO grade IV)
• Pathologically confirmed and imaging-defined recurrent glioma
• ECOG score of 0-2
• Age >=18 years
• Male or female
• Life expectancy >3 months

Exclusion Criteria:

• Severe immune suppression or autoimmune diseases
• Severe cardiac, liver, kidney, or other major organ dysfunction
• Pregnant or breastfeeding women
• Prior treatment with immune checkpoint inhibitors or other immunotherapies
• Other conditions posing significant risk to the patient or preventing adherence to the study protocol

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: Single Treatment Arm; Participants with recurrent malignant glioma will receive IL13Rα2 CAR-T cells secreting anti-PD-L1 antibody within a single-arm, open-label study framework. Two administration strategies are planned according to investigator assessment and protocol procedures: peripheral intravenous infusion alone, or peripheral intravenous infusion combined with intraventricular injection. Dose escalation is planned, including 1×10^6 cells/kg, 3×10^6 cells/kg, and 1×10^7 cells/kg for peripheral infusion. For the combined administration strategy, the intraventricular dose is 20%-30% of the peripheral dose, adjusted according to tolerability.

Biological: IL13Rα2 CAR-T Cells Secreting Anti-PD-L1 Antibody; Autologous IL13Rα2-targeted CAR-T cells engineered to secrete anti-PD-L1 antibody will be administered after lymphodepleting pretreatment. The study includes peripheral intravenous infusion alone or peripheral intravenous infusion combined with intraventricular injection. Peripheral dose-escalation levels are 1×10^6 cells/kg, 3×10^6 cells/kg, and 1×10^7 cells/kg. In the combined administration strategy, the intraventricular dose is 20%-30% of the peripheral dose, with adjustment based on patient tolerability. Patients will be monitored in the ICU or a dedicated inpatient setting during infusion and for adverse events including CRS and ICANS after infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Grade 3 or Higher Treatment-Related Adverse Events	Incidence of Grade 3 or higher treatment-related adverse events after infusion of IL13Rα2 CAR-T cells secreting anti-PD-L1 antibody, including serious adverse events. Adverse event severity will be graded according to CTCAE version 5.0.	From first CAR-T cell infusion through Day 28
Progression-Free Survival	Progression-free survival, defined as the time from first CAR-T cell infusion to documented disease progression or death from any cause, whichever occurs first.	Up to 2 years after first CAR-T cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Maximum Grade of Cytokine Release Syndrome	Incidence and maximum grade of cytokine release syndrome following CAR-T cell infusion, graded according to ASTCT consensus criteria.	From first CAR-T cell infusion through Day 28
Incidence and Maximum Grade of Immune Effector Cell-Associated Neurotoxicity Syndrome	Incidence and maximum grade of immune effector cell-associated neurotoxicity syndrome following CAR-T cell infusion, graded according to ASTCT consensus criteria.	From first CAR-T cell infusion through Day 28
Overall Survival	Overall survival, defined as the time from first CAR-T cell infusion to death from any cause.	Up to 2 years after first CAR-T cell infusion
Objective Response Rate by MRI/PET-CT	Objective response rate, defined as the proportion of participants achieving complete response or partial response based on imaging assessment using multimodal MRI and/or PET-CT.	Assessed at Day 56, Day 84, and every 3 months thereafter up to 2 years
Change in Tumor Volume on Imaging	Change in tumor volume from baseline measured by multimodal MRI and/or PET-CT.	Baseline, Day 7, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years
Change in Quality of Life Score Measured by EORTC QLQ-C30	Change from baseline in quality of life as assessed by the EORTC QLQ-C30 questionnaire.	Baseline, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years
Change in Karnofsky Performance Status Score	Change from baseline in Karnofsky Performance Status score.	Baseline, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years
Change in Modified Rankin Scale Score	Change from baseline in modified Rankin Scale score.	Baseline, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years
Persistence of CAR-T Cells in Peripheral Blood	Persistence of IL13Rα2 CAR-T cells in peripheral blood measured by flow cytometry and/or real-time PCR.	Baseline and multiple post-infusion time points through 2 years
Persistence of CAR-T Cells in Cerebrospinal Fluid	Persistence of IL13Rα2 CAR-T cells in cerebrospinal fluid, when available, is measured by flow cytometry and/or real-time PCR.	Post-infusion time points through 2 years

Collaborators and Investigators

• Sponsor: Ming Yang
• Collaborators: Pecking Union Medical College Hospital, Department of Neurosurgery; Emergency General Hospital, Department of Neurosurgery; Peking University International Hospital, Department of Neurosurgery

Publications and helpful links

General Publications

• Li X,Shang X,Liu J,Zhang Y,Jia X,Li H,Wang Y,Gao J,Ma X,Zhang X,Rong X,Gan W,Zhang Y,Chen J,Wang L,Bao Z,He L,Yan X,Liu Y,Shao J,Xiao Z,Wang Z,Zhu H,Wang Z,Wu Y,Huang Y
• Law I,Albert NL,Arbizu J,Boellaard R,Drzezga A,Galldiks N,la Fougère C,Langen KJ,Lopci E,Lowe V,McConathy J,Quick HH,Sattler B,Schuster DM,Tonn JC,Weller M
• Long AH,Haso WM,Shern JF,Wanhainen KM,Murgai M,Ingaramo M,Smith JP,Walker AJ,Kohler ME,Venkateshwara VR,Kaplan RN,Patterson GH,Fry TJ,Orentas RJ,Mackall CL
• Portnow J,Wang D,Blanchard MS,Tran V,Alizadeh D,Starr R,Dodia R,Chiu V,Brito A,Kilpatrick J,McNamara P,Forman SJ,Badie B,Synold TW,Brown CE

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Immunotherapy; Recurrent Malignant Glioma; IL13Rα2 CAR-T; PD-L1-secreting CAR-T
• 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: NCC5972; 2024-I2M-3-014 (Other Grant/Funding Number: CAMS Medical Innovation Fund)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: At this stage, we have not made definitive plans to share individual participant data (IPD). However, data will be made available to qualified researchers upon request after the completion of the study and publication of the results, subject to applicable privacy and ethical guidelines.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No