Treatment for recurrent glioblastoma using engineered T cells

Phase 1, Open-label Study Evaluating the Safety and Feasibility of CART-EGFR-IL13Ra2 Cells in Patients With EGFR-Amplified Recurrent Glioblastoma

This study is testing a new treatment using specially modified immune cells to see if they can help people with recurrent glioblastoma that has certain protein changes.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (Academic / other)
• Drugs / interventions: bevacizumab, prednisone, CART
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT05168423 on ClinicalTrials.gov

What this trial studies

This open-label phase 1 study evaluates the safety and feasibility of using autologous T cells that express two CARs targeting specific proteins in patients with recurrent glioblastoma that has amplified EGFR. The study consists of a dose escalation phase to determine the maximum tolerated dose (MTD) of these engineered T cells, followed by a dose exploration phase to identify a recommended dose for further testing. Participants will receive CART-EGFR-IL13Ra2 cells after meeting specific eligibility criteria, including prior treatment history and tumor characteristics.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with recurrent, EGFR-amplified glioblastoma that has not responded to prior radiotherapy.

Not a fit: Patients with glioblastoma that does not have EGFR amplification or those who have not undergone prior radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with recurrent glioblastoma, potentially improving survival outcomes.

How similar studies have performed: Other studies using CAR T-cell therapies for glioblastoma have shown promise, indicating potential for success with this novel approach.

Eligibility 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 radiotherapy. 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. Surgical tumor resection for disease control/management or tumor biopsy to confirm tumor recurrence 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 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
7. Karnofsky Performance Status ≥ 60%.
8. Subjects of reproductive potential must agree to use acceptable birth control methods.

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).

Where this trial is running

Philadelphia, Pennsylvania

• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Stephen Bagley, MD, MSCE — University of Pennsylvania
• Study coordinator: Abramson Cancer Center Clinical Trials Service

Conditions Glioblastoma