CART-EGFR-IL13Ra2 in EGFR Amplified Recurrent GBM

• Status: Not yet recruiting
• Trial end date: 2039-12-19
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label phase 1 study to assess the safety and feasibility of autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL13Ra2 (referred to as "CART-EGFR-IL13Ra2 cells") in patients with EGFR-amplified glioblastoma, IDH-wildtype that has recurred following prior radiotherapy.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania
• Collaborator: Tmunity Therapeutics
• Treatments: Cyclophosphamide; Fludarabine; Isotretinoin

Criteria

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, at least 12 weeks 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. 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 upper limit of normal range and total bilirubin ≤ 2.0 mg/dl, except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome (≤ 3.0 mg/dl).

3. Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA

4. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air

6. Karnofsky Performance Status ≥ 60%.

7. 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 enrollment.

7. Dependence on systemic steroids for management of symptoms associated with GBM and associated cerebral edema. Patients must not have an ongoing requirement for dexamethasone.

8. 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.

9. Pregnant or nursing (lactating) women.

10. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).