Locally delivered EGFR/IL13Rα2 CAR T-cell therapy for recurrent high-grade gliomas

A Phase 1 Trial to Evaluate the Safety of EGFR/IL13Rα2 Pool-CAR T Cells in Patients With Recurrent or Progressive High-Grade Glioma (HGG)

This phase I study tests whether a patient's own EGFR/IL13Rα2 CAR T cells, given directly into the brain, are safe and can help adults with recurrent or progressive high-grade gliomas.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: City of Hope Medical Center (Academic / other)
• Drugs / interventions: tocilizumab, bevacizumab, CAR T, radiation, chimeric antigen receptor
• Locations: 1 site (Duarte, California)
• Trial ID: NCT07544992 on ClinicalTrials.gov

What this trial studies

This Phase 1, dose-finding trial uses autologous T cells engineered with CARs against EGFR and IL13Rα2 that are administered locoregionally via a thin flexible catheter placed into the brain. The primary goal is to define safety and the maximum tolerated dose, while secondary endpoints include disease control rate, response rates, time to progression, and 12-month overall survival among patients who receive planned doses. Participants undergo leukapheresis to collect T cells, manufacturing of the dual-targeted CAR T product, and one or more intracranial infusions with serial clinical and imaging monitoring. Exploratory analyses will measure cytokines and immune and tumor microenvironment markers in CSF, tumor cavity fluid, and blood and relate them to adverse events and outcomes.

Who should consider this trial

Good fit: Adults (≥18 years) with radiographic recurrence or progression of IDH-wildtype glioblastoma or grade 4 IDH-mutant astrocytoma, adequate performance status (KPS ≥70 or ECOG ≤2), and who can undergo leukapheresis and intracranial catheter infusion are the intended candidates.

Not a fit: Patients with poor functional status, widespread or non-measurable disease, active uncontrolled infection, inability to undergo leukapheresis or intracranial catheter placement, or who are too close to prior radiation (per protocol timing) are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could offer a targeted immunotherapy that controls tumor growth in some patients with recurrent high-grade gliomas and possibly extends survival.

How similar studies have performed: Early-phase CAR T cell trials in glioma targeting single antigens have produced occasional radiographic responses with manageable safety but limited durable control, making this locoregional dual-targeting approach novel and only preliminarily explored.

Eligibility criteria

Main Inclusion Criteria

* Documented informed consent of the participant and/or legally authorized representative.
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with Study PI approval.
* Age 18 years and older.
* KPS ≥ 70%, ECOG ≤ 2 (Appendix A).
* Life expectancy ≥ 4 weeks.
* Participant has a prior histologically confirmed diagnosis of a glioblastoma (IDH-wildtype) or grade 4 IDH-mutant astrocytoma, or has a prior histologically confirmed diagnosis of a grade 2 or 3 astrocytoma and now has radiographic progression consistent with grade 4 IDH-mutant astrocytoma.
* Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy (such as temozolomide with or without Optune device), and ≥ 12 weeks after completion of front-line radiation therapy.
* COH Clinical Pathology assessment at the initial tumor presentation or recurrent disease (reference Appendix B):

  * IL13Rα2+ expression by IHC \> 20, and
  * EGFR gene-altered by NGS or FISH analysis
* No known contraindications to leukapheresis, steroids, imaging studies, or tocilizumab.
* WBC \> 2000 /dl (or ANC ≥ 1,000/mm3)
* Platelets ≥ 75,000/mm3
* Hemoglobin \> 8g/dL
* Total bilirubin ≤ 1.5x ULN
* AST ≤ 2.5x ULN
* ALT ≤ 2.5x ULN
* Serum creatinine ≤1.6 mg/dL
* O2 saturation ≥ 95% on room air.
* Seronegative for HIV Ag/Ab combo, HCV, and active HBV
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test.
* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of CAR T cells.

Main Exclusion Criteria

* Owing to higher frequency of wound-related complications, participants who require active bevacizumab therapy at the time of enrollment are excluded.
* Participant has not yet recovered from toxicities of prior therapy.
* Participant has received any live vaccine within 30 days prior to enrollment.
* Uncontrolled seizure activity and/or clinically evident progressive encephalopathy.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
* Clinically significant uncontrolled illness.
* Active autoimmune disease requiring systemic immunosuppressive therapy
* Active infection requiring IV antibiotics (for example, minor scalp infection is not exclusion).
* Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection.
* Other active malignancy.
* Females only: Pregnant or breastfeeding.
* Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures.
* Prospective participants who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Where this trial is running

Duarte, California

• City of Hope Medical Center — Duarte, California, United States (Recruiting)

Study contacts

• Principal investigator: Behnam Badie — City of Hope Medical Center

Conditions Recurrent Astrocytoma, IDH-Mutant, Grade 4; Recurrent Glioblastoma, IDH-Wildtype