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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Active Comparator | Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion. |
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| Arm B | Active Comparator | Subjects will receive repeated dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion. |
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| Arm C | Active Comparator | Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 in the pre-operative setting. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CART-EGFR-IL13Ra2 T cells | Biological | CART-EGFR-IL13Ra2 cells are autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL13Ra2. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the feasibility of different approaches for CART-EGFR-IL13Ra2 dosing | Proportion of eligible subjects who receive study treatment. Proportion of eligible subjects assigned to arm B who receive all planned doses of CART-EGFR-IL13Ra2 cells | Up to 2 years |
| Progression-free Survival (PFS) |
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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:
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Abramson Cancer Center Clinical Trials, MD, MSCE | Contact | 215-349-8245 | PMCancerResearch@pennmedicine.upenn.edu | |
| University of Pennsylvania | Contact | PMCancerResearch@pennmedicine.upenn.edu |
| Name | Affiliation | Role |
|---|---|---|
| Stephen Bagley, MD, MSCE | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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This study will evaluate three different approaches for administering CART-EGFR-IL13Ra2 cells in the setting of recurrent glioblastoma. Each dosing approach will be evaluated as a separate treatment arm as outlined below:
Subjects will be assigned to each treatment arm sequentially according to their planned treatment date, starting with Arm C. Once Arm C is fully enrolled, enrollment into Arm A may commence. Once Arm A is fully enrolled and all required safety evaluations have been completed, an interim review of the Arm A data will be performed and evaluated in combination with cumulative CART-EGFR-IL13Ra2 experience from other studies. The results of this interim data review will be evaluated by the Clinical PI and Sponsor Medical Director and used to determine whether Treatment Arm
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Per RANO 2.0 criteria |
| Up to 15 years following CART-EGFR-IL13Ra2 administration |
| Overall Survival (OS) | Per RANO 2.0 criteria | Up to 15 years following CART-EGFR-IL13Ra2 administration |
| Objective Response Rate (ORR) | Per RANO 2.0 criteria in participants with measurable disease at the time of study treatment (Treatment Arms A and B) or Post-Surgical Resection (Treatment Arm C) | Up to 15 years following CART-EGFR-IL13Ra2 administration |
| Duration of response (DOR) | Per RANO 2.0 criteria in participants with measurable disease at the time of study treatment (Treatment Arms A and B) or Post-Surgical Resection (Treatment Arm C) | Up to 15 years following CART-EGFR-IL13Ra2 administration |
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |