Phase 1 Open-label Study Evaluating the Safety of CART-EGFR-IL13Rα2 Cells in Patients With Newly Diagnosed, EGFR-Amplified, MGMT-unmethylated Glioblastoma Following Completion of Initial Radiotherapy
University of Pennsylvania
Summary
This is an open-label phase 1 study to assess the safety, feasibility, pharmacokinetics and preliminary efficacy 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 newly diagnosed, EGFR-amplified, MGMT-unmethylated glioblastoma, without evidence of disease recurrence/progression following completion of initial radiotherapy.
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Step #1 Inclusion Criteria: 1. Signed informed consent form 2. Male or females age ≥ 18 years. 3. Patients with newly diagnosed, EGFR-amplified, MGMT-unmethylated glioblastoma (as defined by WHO 2021 Classification for CNS Tumors, including that the tumor must be IDH wildtype). The tumor must also have histopathologic evidence of glioblastoma (i.e., presence of microvascular proliferation and/or necrosis). 4. Patients must have undergone maximal safe resection of the tumor as per routine cancer care. Patients who have had a biopsy only are not eligible. 5. Tumor tissue positive for wild-type…
Interventions
- DrugCART-EGFR-IL13Ra2 cells
autologous T cells transduced with a bicistronic lentiviral vector containing a murine scFv targeting EGFR epitope 806 and a humanized scFv targeting IL13Ra2; both scFvs are fused to the 4-1BB and CD3ζ signaling domains.
- BiologicalRituximab or Rituximab biosimilar
375 mg/m2/day x 1 day
- DrugFludarabine + Cyclophosphamide combination
Fludarabine: 30mg/m2/day x 3 days; Cyclophosphamide: 300mg/m2/day x 3 days
Location
- University of PennsylvaniaPhiladelphia, Pennsylvania