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

Phase Ib, Open-Label Study of CART-EGFR-IL13Rα2 Cells Administered Following Lymphodepleting Chemotherapy or Prior to Surgical Resection in Patients With EGFR-Amplified Recurrent Glioblastoma

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.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Biological: CART-EGFR-IL13Ra2 T cells

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Abramson Cancer Center Clinical Trials, MD, MSCE; Phone Number: 215-349-8245; Email: PMCancerResearch@pennmedicine.upenn.edu
• Study Contact Backup: Name: University of Pennsylvania; Email: PMCancerResearch@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Abramson Cancer Center Clinical Trials Service; Phone Number: 215-349-8245; Email: PMCancerResearch@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

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

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion.	Biological: 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.
Active Comparator: Arm B; Subjects will receive repeated dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion.	Biological: 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.
Active Comparator: Arm C; Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 in the pre-operative setting.	Biological: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V5.0	Type, frequency, severity, and attribution of adverse events	Up to 15 years following CART-EGFR-IL13Ra2 administration
Occurrence of treatment-limiting toxicities (Arms A and B only)	Type, frequency, severity, and attribution of treatment limiting adverse events as defined in protocol section 8.1.7	Up to 28 days following CART-EGFR-IL13Ra2 administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Per RANO 2.0 criteria	Up to 15 years following CART-EGFR-IL13Ra2 administration
Evaluate the feasibility of different approaches for CART-EGFR-IL13Ra2 dosing	Proportion of eligible subjects who receive study treatment. Proportion of eligible subjects assigned to arm B who receive all planned doses of CART-EGFR-IL13Ra2 cells	Up to 2 years
Overall Survival (OS)	Per RANO 2.0 criteria	Up to 15 years following CART-EGFR-IL13Ra2 administration
Objective Response Rate (ORR)	Per RANO 2.0 criteria in participants with measurable disease at the time of study treatment (Treatment Arms A and B) or Post-Surgical Resection (Treatment Arm C)	Up to 15 years following CART-EGFR-IL13Ra2 administration
Duration of response (DOR)	Per RANO 2.0 criteria in participants with measurable disease at the time of study treatment (Treatment Arms A and B) or Post-Surgical Resection (Treatment Arm C)	Up to 15 years following CART-EGFR-IL13Ra2 administration

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Stephen Bagley, MD, MSCE, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2025
• Primary Completion (Estimated): November 1, 2042
• Study Completion (Estimated): November 1, 2042

Study Registration Dates

• First Submitted: September 30, 2025
• First Submitted That Met QC Criteria: September 30, 2025
• First Posted (Actual): October 6, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 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: 10325 (Fred Hutch/University of Washington Cancer Consortium)

Drug and device information, study documents

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