CART-EGFR-IL13Ra2 in EGFR Amplified Recurrent GBM

Phase

Condition

Gliomas

Astrocytoma

Treatment

CART-EGFR-IL13Ra2 Cells

Clinical Study ID

NCT05168423

16321

Ages > 18
All Genders

Study 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. This study will take place in two parts: an initial dose escalation phase followed by a dose exploration phase. In the dose expansion phase, the maximum tolerated dose (MTD) of CART-EGFR-IL13Ra2 cells will be determined using a standard 3+3 design. Once the MTD has been determined, the dose exploration phase will allow for further identification of a recommended dose for expansion (RDE) as well as the safety and feasibility of alternative dosing schedules.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Signed, written informed consent
Male or female age ≥ 18 years
Patients with glioblastoma, IDH-wildtype (as defined by WHO 2021 Classification ofCNS Tumors) that has recurred following prior radiotherapy. For patients with tumorsharboring methylation of the MGMT promoter, at least 12 weeks must have elapsedsince completion of first-line radiotherapy.
Tumor tissue positive for wild-type EGFR amplification by NeoGenomics Laboratories.Archival tumor from patient's initial surgery at time of original diagnosis orrecently collected tumor from time of recurrence are acceptable.
Surgical tumor resection for disease control/management or tumor biopsy to confirmtumor recurrence is clinically indicated in the opinion of thephysician-investigator.
Adequate organ function defined as:
Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 30 ml/min andnot on dialysis.
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'ssyndrome (≤ 3.0 mg/dl).
Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea andpulse oxygen > 92% on room air
Karnofsky Performance Status ≥ 60%.
Subjects of reproductive potential must agree to use acceptable birth controlmethods.

Exclusion

Exclusion Criteria:

Active hepatitis B or hepatitis C infection.
Any other active, uncontrolled infection.
Class III/IV cardiovascular disability according to the New York Heart AssociationClassification.
Tumors primarily localized to the brain stem or spinal cord.
Severe, active co-morbidity in the opinion of the physician-investigator that wouldpreclude participation in this study.
Receipt of bevacizumab within 3 months prior to physician-investigator confirmationof eligibility.
Active autoimmune disease requiring systemic immunosuppressive treatment equivalentto ≥ 10 mg daily of prednisone. Patients with autoimmune neurological diseases (suchas MS or Parkinson's) will be excluded.
Patients who are pregnant or nursing (lactating).
History of allergy or hypersensitivity to study product excipients (human serumalbumin, DMSO, and Dextran 40).

Study Design