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

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат 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.

Первичные конечные точки

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

Вторичные конечные точки (5)

• Evaluate the feasibility of different approaches for CART-EGFR-IL13Ra2 dosing [Срок оценки: Up to 2 years]
• Progression-free Survival (PFS) [Срок оценки: Up to 15 years following CART-EGFR-IL13Ra2 administration]
• Overall Survival (OS) [Срок оценки: Up to 15 years following CART-EGFR-IL13Ra2 administration]
• Objective Response Rate (ORR) [Срок оценки: Up to 15 years following CART-EGFR-IL13Ra2 administration]
• Duration of response (DOR) [Срок оценки: Up to 15 years following CART-EGFR-IL13Ra2 administration]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Pennsylvania — Philadelphia

Идентификаторы

NCT: NCT07209241 · 10325

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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