Different Approaches for CART-EGFR-IL13Ra2 Dosing in Recurrent GBM

NCT ID: NCT07209241

Last Updated: 2025-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-03

Study Completion Date

2042-11-01

Brief Summary

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This is an open-label, phase 1b study to evaluate different approaches for CART-EGFR-IL13Ra2 dosing and further characterize the safety, feasibility, preliminary efficacy, and pharmacokinetics of CART-EGFR-IL13Ra2 cells in patients with EGFR-amplified glioblastoma that has recurred following prior radiotherapy.

Detailed Description

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Conditions

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Recurrent Glioblastoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

This study will evaluate three different approaches for administering CART-EGFR-IL13Ra2 cells in the setting of recurrent glioblastoma. Each dosing approach will be evaluated as a separate treatment arm as outlined below:

* Arm A: Single Fixed-Dose Administration Following Lymphodepletion
* Arm B: Repeat Dose Administration Following Lymphodepletion
* Arm C: Single Fixed-Dose Administration in the Pre-Operative Setting

Subjects are assigned sequentially, beginning with Arm A. Once Arm A is fully enrolled and all safety evaluations are complete, the data, along with cumulative data from other CART-EGFR-IL13Ra2 studies, will be reviewed by the Clinical Principal Investigator (PI) and Sponsor Medical Director to determine whether to open Arm B.

If it is decided not to progress to Arm B for any reason, Arm A will be expanded to include up to a total of eight evaluable subjects. Enrollment into Arm C begins only after Arms A and B (if applicable) are fully enrolled.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A

Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion.

Group Type ACTIVE_COMPARATOR

CART-EGFR-IL13Ra2 T cells

Intervention Type BIOLOGICAL

CART-EGFR-IL13Ra2 cells are autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL13Ra2.

Arm B

Subjects will receive repeated dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion.

Group Type ACTIVE_COMPARATOR

CART-EGFR-IL13Ra2 T cells

Intervention Type BIOLOGICAL

CART-EGFR-IL13Ra2 cells are autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL13Ra2.

Arm C

Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 in the pre-operative setting.

Group Type ACTIVE_COMPARATOR

CART-EGFR-IL13Ra2 T cells

Intervention Type BIOLOGICAL

CART-EGFR-IL13Ra2 cells are autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL13Ra2.

Interventions

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CART-EGFR-IL13Ra2 T cells

CART-EGFR-IL13Ra2 cells are autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL13Ra2.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Signed, written informed consent
2. Male or female age ≥ 18 years
3. Patients with glioblastoma, IDH-wildtype (as defined by WHO 2021 Classification of CNS Tumors) that has recurred following prior radiotherapy1. For patients with tumors harboring methylation of the MGMT promoter, a t l east 1 2 w eeks must have elapsed since completion of first-line radiotherapy.
4. Tumor tissue positive for wild-type EGFR amplification by NeoGenomics Laboratories. Archival tumor from patient's initial surgery at time of original diagnosis or recently collected tumor from time of recurrence are acceptable.
5. Surgical tumor resection for disease control/management (Arms A, B, C) or tumor biopsy to confirm tumor recurrence (Arms A and B only) is clinically indicated in the opinion of the physician-investigator.
6. Adequate organ function defined as:

1. Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 30 ml/min and not on dialysis.
2. ALT/AST ≤ 3 x ULN
3. Total bilirubin ≤ 2.0 mg/dL, except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome (≤ 3.0 mg/dL)
4. Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA
5. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air
7. Karnofsky Performance Status ≥ 60%.
8. Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.

Exclusion Criteria

1. Active hepatitis B or hepatitis C infection.
2. Any other active, uncontrolled infection.
3. Class III/IV cardiovascular disability according to the New York Heart Association Classification
4. Tumors primarily localized to the brain stem or spinal cord.
5. Severe, active co-morbidity in the opinion of the physician-investigator that would preclude participation in this study.
6. Receipt of bevacizumab within 3 months prior to physician-investigator confirmation of eligibility.
7. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10 mg daily of prednisone. Patients with autoimmune neurological diseases (such as MS or Parkinson's) will be excluded.
8. Patients who are pregnant or nursing (lactating).
9. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Pennsylvania

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen Bagley, MD, MSCE

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

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University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Abramson Cancer Center Clinical Trials, MD, MSCE

Role: CONTACT

215-349-8245

University of Pennsylvania

Role: CONTACT

Facility Contacts

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Abramson Cancer Center Clinical Trials Service

Role: primary

215-349-8245

Other Identifiers

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10325

Identifier Type: -

Identifier Source: org_study_id

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