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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
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 Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.

Recruiting Locations

University of Pennsylvania
Philadelphia 4560349, Pennsylvania 6254927 19104
Contact:
Abramson Cancer Center Clinical Trials Service
215-349-8245
PMCancerResearch@pennmedicine.upenn.edu

More Details

Status
Recruiting
Sponsor
University of Pennsylvania

Study Contact

Abramson Cancer Center Clinical Trials, MD, MSCE
215-349-8245
PMCancerResearch@pennmedicine.upenn.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.