RECRUITING

CART-EGFR-IL13Ra2 in Newly Diagnosed GBM Following Initial Radiotherapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is an open-label phase 1 study to assess the safety, feasibility, pharmacokinetics and preliminary efficacy of autologous T cells co-expressing two CARs targeting the cryptic EGFR epitope 806 and IL3Ra2 (referred to as "CART-EGFR-IL13Ra2 cells"). Patients with newly diagnosed, EGFR-amplified, MGMT-unmethylated glioblastoma who have undergone maximal safe surgical resection will be approached for initial study participation. A two-step screening/eligibility process will be utilized. Following informed consent, subjects who meet Step #1 Eligibility Criteria will remain on study and complete a course of radiotherapy (60 Gy) without temozolomide as per their routine cancer care. If there is no overt evidence of disease recurrence/progression following radiotherapy, additional screening tests/procedures will be performed. Subjects who then meet Step #2 Eligibility Criteria will undergo apheresis collection to initiate cell product manufacturing and surgical placement of a CSF-Ventricular Reservoir to allow for intracerebroventricular injection of the CART-EGFR-IL13Ra2 cells. All subjects will receive a single fixed dose of CART-EGFR-IL13Ra2 cells on Day 0 via intracerebroventricular delivery.

Official Title

Phase 1 Open-label Study Evaluating the Safety of CART-EGFR-IL13Rα2 Cells in Patients With Newly Diagnosed, EGFR-Amplified, MGMT-unmethylated Glioblastoma Following Completion of Initial Radiotherapy

Quick Facts

Study Start:2025-07-09

Study Completion:2042-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06973096

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Signed informed consent form 2. Male or females age ≥ 18 years. 3. Patients with newly diagnosed, EGFR-amplified, MGMT-unmethylated glioblastoma (as defined by WHO 2021 Classification for CNS Tumors, including that the tumor must be IDH wildtype). The tumor must also have histopathologic evidence of glioblastoma (i.e., presence of microvascular proliferation and/or necrosis). 4. Patients must have undergone maximal safe resection of the tumor as per routine cancer care. Patients who have had a biopsy only are not eligible. 5. Tumor tissue positive for wild-type EGFR amplification by Neogenomics Laboratories 6. Karnofsky Performance Status ≥ 60% 7. Patient scheduled to receive 60 Gy of radiotherapy. Either photon or proton therapy is acceptable.	1. Active hepatitis B or hepatitis C infection 2. Class III/IV cardiovascular disability according to the New York Heart Association Classification. 3. Tumors with enhancing disease involving the thalamus, brain stem or spinal cord. 4. Tumors with an MGMT promoter methylation result of hypermethylated, methylated, low positive methylated, or indeterminate. 5. Multifocal disease if ≥ 1 focus of tumor has not undergone maximal safe resection 6. Severe, active co-morbidity that, in the opinion of the physician-investigator, would preclude participation in this study. 7. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40). 8. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded. 9. Anticipated treatment plan that involves bevacizumab, any other systemic anti-neoplastic therapy, and/or tumor-treating fields as part of 1st line therapy.

Inclusion Criteria

Exclusion Criteria

1. Signed informed consent form
2. Male or females age ≥ 18 years.
3. Patients with newly diagnosed, EGFR-amplified, MGMT-unmethylated glioblastoma (as defined by WHO 2021 Classification for CNS Tumors, including that the tumor must be IDH wildtype). The tumor must also have histopathologic evidence of glioblastoma (i.e., presence of microvascular proliferation and/or necrosis).
4. Patients must have undergone maximal safe resection of the tumor as per routine cancer care. Patients who have had a biopsy only are not eligible.
5. Tumor tissue positive for wild-type EGFR amplification by Neogenomics Laboratories
6. Karnofsky Performance Status ≥ 60%
7. Patient scheduled to receive 60 Gy of radiotherapy. Either photon or proton therapy is acceptable.

1. Active hepatitis B or hepatitis C infection
2. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
3. Tumors with enhancing disease involving the thalamus, brain stem or spinal cord.
4. Tumors with an MGMT promoter methylation result of hypermethylated, methylated, low positive methylated, or indeterminate.
5. Multifocal disease if ≥ 1 focus of tumor has not undergone maximal safe resection
6. Severe, active co-morbidity that, in the opinion of the physician-investigator, would preclude participation in this study.
7. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
8. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
9. Anticipated treatment plan that involves bevacizumab, any other systemic anti-neoplastic therapy, and/or tumor-treating fields as part of 1st line therapy.

Contacts and Locations

Study Contact

Abramson Cancer Center Clinical Trials Service

CONTACT

215-349-8245

PMCancerResearch@pennmedicine.upenn.edu

Principal Investigator

Stephen Bagley, MD, MSCE

PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Study Locations (Sites)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: University of Pennsylvania

Stephen Bagley, MD, MSCE, PRINCIPAL_INVESTIGATOR, University of Pennsylvania

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07-09

Study Completion Date2042-07

Study Record Updates

Study Start Date2025-07-09

Study Completion Date2042-07

Terms related to this study

Additional Relevant MeSH Terms

Glioblastoma