Different dosing approaches for CAR-T cells that target EGFR and IL13Ra2 in recurrent glioblastoma.

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 trial tests whether different dosing strategies of CAR-T cells targeting EGFR and IL13Ra2 are safe and workable for adults with EGFR‑amplified recurrent glioblastoma.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (other)
• Drugs / interventions: bevacizumab, prednisone, CART
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT07209241 on ClinicalTrials.gov

What this trial studies

This open-label Phase 1b trial tests several dosing approaches of autologous CART-EGFR-IL13Ra2 T cells to define safety, feasibility, preliminary anti-tumor activity, and pharmacokinetics. Eligible adults have IDH‑wildtype glioblastoma that has recurred after prior radiotherapy and whose tumor shows wild-type EGFR amplification. Participants must undergo surgical resection or biopsy as part of treatment and monitoring, with close clinical and laboratory follow-up for toxicity and tumor response. The trial is run at a single site (University of Pennsylvania) and focuses on early safety and dosing optimization rather than definitive efficacy.

Who should consider this trial

Good fit: Adults (≥18) with IDH‑wildtype glioblastoma that has recurred after radiotherapy, documented wild-type EGFR amplification, adequate organ function, and who can undergo surgical resection or biopsy are the intended participants.

Not a fit: Patients whose tumors lack EGFR amplification, who cannot undergo the required surgery/biopsy, or who have poor organ function or significant comorbidities are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, optimized dosing of this dual-targeted CAR-T therapy could shrink tumors or slow progression and potentially extend survival for patients with EGFR‑amplified recurrent glioblastoma.

How similar studies have performed: Previous CAR-T trials in glioblastoma have produced occasional tumor responses but generally limited durable control, so this dual-targeted dosing approach is largely novel and unproven.

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 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).

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, MD, MSCE

Conditions: Recurrent Glioblastoma