CART-EGFR-IL13Ra2 in EGFR Amplified Recurrent GBM

University of Pennsylvania

Status and phase: Enrolling; Phase 1

Conditions: Glioblastoma

Treatments: Drug: CART-EGFR-IL13Ra2 Cells

Study type: Interventional

Funder types: Other

Identifiers

NCT05168423

16321

Details and patient eligibility

About

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.

Enrollment: 21 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 radiotherapy. For patients with tumors harboring methylation of the MGMT promoter, at least 12 weeks 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 or tumor biopsy to confirm tumor recurrence 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 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).
   3. Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA
   4. 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.

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 5 patient groups

Cohort 1

Experimental group

Description:

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

Treatment:

Drug: CART-EGFR-IL13Ra2 Cells

Cohort -1

Experimental group

Description:

Participants will receive a single fixed dose of 5x10\^6 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.

Treatment:

Drug: CART-EGFR-IL13Ra2 Cells

Cohort 2

Experimental group

Description:

Participants will receive a single fixed dose of 2.5x10\^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.

Treatment:

Drug: CART-EGFR-IL13Ra2 Cells

Cohort 3

Experimental group

Description:

Participants will receive a single fixed dose of 5x10\^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.

Treatment:

Drug: CART-EGFR-IL13Ra2 Cells

Cohort 4

Experimental group

Description:

Participants will receive two doses of CART-EGFR-IL13Rα2 cells, to determine the optimal dose schedule.

Treatment:

Drug: CART-EGFR-IL13Ra2 Cells