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

NCT06973096 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 03325
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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 IL13Ra2 (referred to as "CART-EGFR-IL13Ra2 cells") in patients with newly diagnosed, EGFR-amplified, MGMT-unmethylated glioblastoma, without evidence of disease recurrence/progression following completion of initial radiotherapy.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• 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 (TLTs)

  28 days post-CAR T cell administration

Secondary Outcomes (7)

• Proportion of enrolled subjects who receive study treatment as planned

  28 days following initial treatment with CART-EGFR-IL13Ra2 cells

• Proportion of eligible subjects who receive study treatment as planned

  28 days following initial treatment with CART-EGFR-IL13Ra2 cells

• Frequency of manufacturing failures

  3 months

• Progression-free Survival (PFS)

  Up to 15 years following CART-EGFR-IL13Ra2 administration

• Overall Survival (OS)

  Up to 15 years following initial CART-EGFR-IL13Ra2 administration

Study Arms (2)

Cohort A (Single Fixed Dose)

EXPERIMENTAL

All subjects will receive a single fixed dose of CART-EGFR-IL13Ra2 cells on Day 0 via intracerebroventricular delivery.

Drug: CART-EGFR-IL13Ra2 cells

Cohort B (Repeat Cycles Following Lymphodepletion)

EXPERIMENTAL

CART-EGFR-IL13Ra2 cells will be administered via intracerebroventricular delivery in q6 week cycles of treatment, following lymphodepletion with fludarabine, cyclophosphamide, and rituximab.

Drug: CART-EGFR-IL13Ra2 cells; Biological: Rituximab or Rituximab biosimilar; Drug: Fludarabine + Cyclophosphamide combination

Interventions

Rituximab or Rituximab biosimilar BIOLOGICAL

375 mg/m2/day x 1 day

Cohort B (Repeat Cycles Following Lymphodepletion)

Fludarabine + Cyclophosphamide combination DRUG

Fludarabine: 30mg/m2/day x 3 days; Cyclophosphamide: 300mg/m2/day x 3 days

Cohort B (Repeat Cycles Following Lymphodepletion)

CART-EGFR-IL13Ra2 cells DRUG

autologous T cells transduced with a bicistronic lentiviral vector containing a murine scFv targeting EGFR epitope 806 and a humanized scFv targeting IL13Ra2; both scFvs are fused to the 4-1BB and CD3ζ signaling domains.

Cohort A (Single Fixed Dose); Cohort B (Repeat Cycles Following Lymphodepletion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form
• Male or females age ≥ 18 years.
• 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).
• 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.
• Tumor tissue positive for wild-type EGFR amplification by Neogenomics Laboratories
• Karnofsky Performance Status ≥ 60%
• Patient scheduled to receive 60 Gy of radiotherapy. Either photon or proton therapy is acceptable.

You may not qualify if:

• Active hepatitis B or hepatitis C infection
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Tumors with enhancing disease involving the thalamus, brain stem or spinal cord.
• Tumors with an MGMT promoter methylation result of hypermethylated, methylated, low positive methylated, or indeterminate.
• Multifocal disease if ≥ 1 focus of tumor has not undergone maximal safe resection
• Severe, active co-morbidity that, in the opinion of the physician-investigator, would preclude participation in this study.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
• Anticipated treatment plan that involves bevacizumab, any other systemic anti-neoplastic therapy, and/or tumor-treating fields as part of 1st line therapy.
• Patient completed full course of radiotherapy to 60 Gy.
• No overt evidence of disease recurrence/progression post-radiotherapy confirmed by RANO 2.0 criteria.
• Karnofsky Performance Status ≥ 60%
• Adequate organ function defined as:
• Serum creatinine ≤ 1.5x ULN or estimated creatinine clearance ≥ 30 mL/min and not on dialysis
• ALT/AST ≤ 3 x ILN

Sponsors & Collaborators

• University of Pennsylvania: lead
• Kite Pharma (a Gilead Company): collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Rituximab; fludarabine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Stephen Bagley, MD, MSCE

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abramson Cancer Center Clinical Trials Service

CONTACT

215-349-8245; PMCancerResearch@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2025
• First Posted: May 15, 2025
• Study Start: July 18, 2025
• Primary Completion (Estimated): July 1, 2042
• Study Completion (Estimated): July 1, 2042
• Last Updated: May 11, 2026

Record last verified: 2026-05

Locations

US (1)