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
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.
Arms & 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
Outcome measures
Primary
Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V5.0
Type, frequency, severity, and attribution of adverse events
Time frame: Up to 15 years following CART-EGFR-IL13Ra2 administration
Occurrence of treatment-limiting toxicities (TLTs)
Time frame: 28 days post-CAR T cell administration
Secondary
Proportion of enrolled subjects who receive study treatment as planned
Time frame: 28 days following initial treatment with CART-EGFR-IL13Ra2 cells
Proportion of eligible subjects who receive study treatment as planned
Time frame: 28 days following initial treatment with CART-EGFR-IL13Ra2 cells
Frequency of manufacturing failures
Time frame: 3 months
Progression-free Survival (PFS)
Time frame: Up to 15 years following CART-EGFR-IL13Ra2 administration
Overall Survival (OS)
Time frame: Up to 15 years following initial CART-EGFR-IL13Ra2 administration
Objective Response Rate (ORR)
Time frame: Up to 12 months following CART-EGFR-IL13Ra2 administration
Duration of response (DOR)
Time frame: Up to 15 years following initial CART-EGFR-IL13Ra2 administration
Eligibility criteria
Study locations (1)
University of Pennsylvania
Philadelphia, Pennsylvania, 19104