Phase 1, Open-label Study Evaluating the Safety and Feasibility of CART-EGFR-IL13Ra2 Cells in Patients With EGFR-Amplified Recurrent Glioblastoma

University of Pennsylvania2 个研究点分布在 1 个国家目标入组 67 人开始时间: 2023年2月24日最近更新: 2026年4月13日

适应症

干预措施

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: University of Pennsylvania
入组人数: 67
试验地点: 2
主要终点: Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V5.0

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

This is a Phase 1 study evaluating the safety and feasibility of CART-EGFR-IL13Ra2 cells in a 3+3 dose escalation design as described below.

• Cohort 1 (N = 3-6): will receive a single fixed dose of 1x10^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0. This dose level will be evaluated as follows:

If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level.
If 0 DLT/3 subjects or 1 DLT/6 subjects occur, the study will advance to Cohort 2.

In the event that 2 or more DLTs occur in Cohort 1, then enrollment into Cohort 1 will be stopped and the dose will be de-escalated to 5x10^6 CART-EGFR-IL13Ra2 cells. This de-escalated cohort will be identified as Cohort -1.

• Cohort -1 (N = 3-6): will receive a single fixed dose of 5x10^6 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0. This dose level will be evaluated as follows:

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Sequential
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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 radiotherapy. For patients with tumors harboring methylation of the MGMT promoter, at least 12 weeks 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 or tumor biopsy to confirm tumor recurrence 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 upper limit of normal range and 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.

排除标准

•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).

研究组 & 干预措施

Cohort 1

Experimental

Participants will receive a single fixed dose of 1x10^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.