CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Signed, written informed consent
2. Male or female age ≥ 18 years
3. 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.
4. 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.
5. 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.
6. Adequate organ function defined as:

   1. Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 30 ml/min and not on dialysis.
   2. ALT/AST ≤ 3 x ULN
   3. Total bilirubin ≤ 2.0 mg/dL, except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome (≤ 3.0 mg/dL)
   4. Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA
   5. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air
7. Karnofsky Performance Status ≥ 60%.
8. Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.

Exclusion Criteria:

1. Active hepatitis B or hepatitis C infection.
2. Any other active, uncontrolled infection.
3. Class III/IV cardiovascular disability according to the New York Heart Association Classification
4. Tumors primarily localized to the brain stem or spinal cord.
5. Severe, active co-morbidity in the opinion of the physician-investigator that would preclude participation in this study.
6. Receipt of bevacizumab within 3 months prior to physician-investigator confirmation of eligibility.
7. 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.
8. Patients who are pregnant or nursing (lactating).
9. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

主要终点：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 · Up to 15 years following CART-EGFR-IL13Ra2 administration；Occurrence of treatment-limiting toxicities (Arms A and B only) · Type, frequency, severity, and attribution of treatment limiting adverse events as defined in protocol section 8.1.7 · Up to 28 days following CART-EGFR-IL13Ra2 administration
次要终点：Evaluate the feasibility of different approaches for CART-EGFR-IL13Ra2 dosing；Progression-free Survival (PFS)；Overall Survival (OS)；Objective Response Rate (ORR)；Duration of response (DOR)

• Arm A · ACTIVE_COMPARATOR · Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion.
• Arm B · ACTIVE_COMPARATOR · Subjects will receive repeated dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion.
• Arm C · ACTIVE_COMPARATOR · Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 in the pre-operative setting.

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.