Different Approaches for CART-EGFR-IL13Ra2 Dosing in Recurrent GBM

Official title

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

Overview

This is an open-label, phase 1b study to evaluate different approaches for CART-EGFR-IL13Ra2 dosing and further characterize the safety, feasibility, preliminary efficacy, and pharmacokinetics of CART-EGFR-IL13Ra2 cells in patients with EGFR-amplified glioblastoma that has recurred following prior radiotherapy.

Interventions

• Biological CART-EGFR-IL13Ra2 T cells
  CART-EGFR-IL13Ra2 cells are autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL13Ra2.

Primary outcome measures

• Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V5.0 [Time frame: Up to 15 years following CART-EGFR-IL13Ra2 administration]
• Occurrence of treatment-limiting toxicities (Arms A and B only) [Time frame: Up to 28 days following CART-EGFR-IL13Ra2 administration]

Secondary outcome measures (5)

• Evaluate the feasibility of different approaches for CART-EGFR-IL13Ra2 dosing [Time frame: Up to 2 years]
• 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 CART-EGFR-IL13Ra2 administration]
• Objective Response Rate (ORR) [Time frame: Up to 15 years following CART-EGFR-IL13Ra2 administration]
• Duration of response (DOR) [Time frame: Up to 15 years following CART-EGFR-IL13Ra2 administration]

Eligibility criteria

Inclusion criteria

• Signed, written informed consent
• Male or female age ≥ 18 years
• 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.
• 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.
• 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.
• Adequate organ function defined as:

• Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 30 ml/min and not on dialysis.
• ALT/AST ≤ 3 x ULN
• Total bilirubin ≤ 2.0 mg/dL, except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome (≤ 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 and pulse oxygen > 92% on room air
• Karnofsky Performance Status ≥ 60%.
• Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.

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 Association Classification
• Tumors primarily localized to the brain stem or spinal cord.
• Severe, active co-morbidity in the opinion of the physician-investigator that would preclude participation in this study.
• Receipt of bevacizumab within 3 months prior to physician-investigator confirmation of eligibility.
• 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.
• Patients who are pregnant or nursing (lactating).
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Pennsylvania — Philadelphia

Identifiers

NCT: NCT07209241 · 10325

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗