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

NCT07209241 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 10325
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Evaluate the feasibility of different approaches for CART-EGFR-IL13Ra2 dosing

  Up to 2 years

• Progression-free Survival (PFS)

  Up to 15 years following CART-EGFR-IL13Ra2 administration

• Overall Survival (OS)

  Up to 15 years following CART-EGFR-IL13Ra2 administration

• Objective Response Rate (ORR)

  Up to 15 years following CART-EGFR-IL13Ra2 administration

• Duration of response (DOR)

  Up to 15 years following CART-EGFR-IL13Ra2 administration

Study Arms (3)

Arm A

ACTIVE COMPARATOR

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

Biological: CART-EGFR-IL13Ra2 T cells

Arm B

ACTIVE COMPARATOR

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

Biological: CART-EGFR-IL13Ra2 T cells

Arm C

ACTIVE COMPARATOR

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

Biological: CART-EGFR-IL13Ra2 T cells

Interventions

CART-EGFR-IL13Ra2 T cells BIOLOGICAL

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

Arm A; Arm B; Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, written informed consent
• Male or female age ≥ 18 years
• 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.
• 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.
• 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.
• Adequate organ function defined as:
• Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 30 ml/min and not on dialysis.
• ALT/AST ≤ 3 x ULN
• Total bilirubin ≤ 2.0 mg/dL, except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome (≤ 3.0 mg/dL)
• Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air
• Karnofsky Performance Status ≥ 60%.
• Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.

You may not qualify if:

• Active hepatitis B or hepatitis C infection.
• Any other active, uncontrolled infection.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification
• Tumors primarily localized to the brain stem or spinal cord.
• Severe, active co-morbidity in the opinion of the physician-investigator that would preclude participation in this study.
• Receipt of bevacizumab within 3 months prior to physician-investigator confirmation of eligibility.
• 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.
• Patients who are pregnant or nursing (lactating).
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Stephen Bagley, MD, MSCE

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abramson Cancer Center Clinical Trials, MD, MSCE

CONTACT

215-349-8245; PMCancerResearch@pennmedicine.upenn.edu

University of Pennsylvania

CONTACT

PMCancerResearch@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 30, 2025
• First Posted: October 6, 2025
• Study Start: December 3, 2025
• Primary Completion (Estimated): November 1, 2042
• Study Completion (Estimated): November 1, 2042
• Last Updated: December 12, 2025

Record last verified: 2025-12

Locations

US (1)