21 Participants Needed

CAR T-cell Therapy for Glioblastoma

AC
Overseen ByAbramson Cancer Center Clinical Trials Service
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on bevacizumab, you must not have received it within 3 months before eligibility confirmation.

What data supports the effectiveness of the treatment CART-EGFR-IL13Ra2 Cells for glioblastoma?

Research shows that CAR T-cell therapy targeting IL13Rα2, a protein found in glioblastoma but not in normal brain tissue, can lead to tumor regression and improved survival in animal models and a patient case study. This suggests that CART-EGFR-IL13Ra2 Cells could be effective in treating glioblastoma by specifically targeting cancer cells without affecting healthy brain cells.12345

Is CAR T-cell therapy for glioblastoma safe for humans?

Research shows that CAR T-cell therapy targeting IL13Rα2 in glioblastoma patients has not been associated with severe toxic effects, indicating it is generally safe in humans.12367

What makes the CAR T-cell therapy for glioblastoma unique?

This treatment uses specially engineered T cells to target a protein called IL13Rα2, which is found on glioblastoma cells but not on normal brain cells, making it a precise and promising approach for attacking the tumor without harming healthy tissue.12358

What is the purpose of this trial?

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.

Research Team

Stephen Bagley, MD, MSCE profile ...

Stephen Bagley, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults over 18 with recurrent glioblastoma, IDH-wildtype, after radiotherapy. Candidates must have adequate organ function, EGFR-amplified tumors confirmed by specific tests, and agree to use birth control. Excluded are those with active hepatitis B/C, severe comorbidities, recent bevacizumab treatment, autoimmune diseases needing high-dose steroids or pregnant/nursing women.

Inclusion Criteria

My glioblastoma has returned after radiation treatment.
Subjects of reproductive potential must agree to use acceptable birth control methods
My doctor recommends surgery or a biopsy to manage or confirm my cancer's return.
See 9 more

Exclusion Criteria

I am allergic to some ingredients in the study medication.
I have not received bevacizumab in the last 3 months.
I have an active hepatitis B or C infection.
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single fixed dose of CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0, with dose escalation based on cohort assignment

4 weeks
1 visit (in-person) for administration, followed by staggered monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, with formal DLT evaluations performed after the 3rd subject in each cohort reaches the Day 28 safety follow-up visit

4 weeks
1 visit (in-person) for safety follow-up

Long-term follow-up

Participants are monitored for progression-free survival and objective response rate over an extended period

15 years

Treatment Details

Interventions

  • CART-EGFR-IL13Ra2 Cells
Trial Overview The study is testing the safety of CART-EGFR-IL13Ra2 cells in patients whose glioblastoma has returned despite prior treatments. It's an early-phase trial where participants receive genetically modified T cells targeting two specific molecules on their cancer.
Participant Groups
5Treatment groups
Experimental Treatment
Group I: Cohort 4Experimental Treatment1 Intervention
Participants will receive two doses of CART-EGFR-IL13Rα2 cells, to determine the optimal dose schedule.
Group II: Cohort 3Experimental Treatment1 Intervention
Participants will receive a single fixed dose of 5x10\^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.
Group III: Cohort 2Experimental Treatment1 Intervention
Participants will receive a single fixed dose of 2.5x10\^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.
Group IV: Cohort 1Experimental Treatment1 Intervention
Participants will receive a single fixed dose of 1x10\^7 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.
Group V: Cohort -1Experimental Treatment1 Intervention
Participants will receive a single fixed dose of 5x10\^6 CART-EGFR-IL13Ra2 cells via intrathecal administration on Day 0.

CART-EGFR-IL13Ra2 Cells is already approved in United States for the following indications:

🇺🇸
Approved in United States as CART-EGFR-IL13Ra2 for:
  • Glioblastoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials
2,118
Recruited
45,270,000+

Tmunity Therapeutics

Industry Sponsor

Trials
7
Recruited
140+

Gilead Sciences

Industry Sponsor

Trials
1,150
Recruited
878,000+
Daniel O'Day profile image

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger profile image

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Kite Pharma (a Gilead Company)

Collaborator

Tmunity Therapeutics, a wholly owned subsidiary of Kite Pharma (a Gilead company)

Collaborator

Trials
2
Recruited
70+

Findings from Research

IL13Rα2-specific CAR T cells, designed to target glioblastoma without affecting normal brain tissue, demonstrated effective recognition and destruction of IL13Rα2-positive cancer cells without cross-reactivity to IL13Rα1.
In vivo studies showed that CAR T cells with short spacer regions and specific endodomains significantly improved survival in mice with glioma, indicating their potential as a promising treatment for glioblastoma and similar cancers.
Characterization and Functional Analysis of scFv-based Chimeric Antigen Receptors to Redirect T Cells to IL13Rα2-positive Glioma.Krenciute, G., Krebs, S., Torres, D., et al.[2018]
The YYB-103 CAR T cells demonstrated selective targeting and toxicity against malignant glioma cells expressing IL13Rα2, while sparing cells that express IL13Rα1, indicating a promising therapeutic approach for treating glioblastoma.
Both intravenous and intracerebroventricular administration of YYB-103 CAR T cells significantly reduced tumor volume and improved survival in mouse models, suggesting effective delivery across the blood-brain barrier and potential for clinical application in patients with recurrent glioblastoma.
Chimeric Antigen Receptor T Cells With Modified Interleukin-13 Preferentially Recognize IL13Rα2 and Suppress Malignant Glioma: A Preclinical Study.Kim, K., Gwak, HS., Han, N., et al.[2021]
A patient with recurrent multifocal glioblastoma treated with IL13Rα2-targeted CAR T cells showed no severe toxic effects (grade 3 or higher) after multiple infusions over 220 days, indicating a favorable safety profile for this therapy.
The treatment resulted in significant tumor regression in both intracranial and spinal tumors, with a sustained clinical response lasting 7.5 months, alongside increased cytokine and immune cell levels in the cerebrospinal fluid, suggesting effective immune activation against the tumor.
Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy.Brown, CE., Alizadeh, D., Starr, R., et al.[2023]

References

Characterization and Functional Analysis of scFv-based Chimeric Antigen Receptors to Redirect T Cells to IL13Rα2-positive Glioma. [2018]
Chimeric Antigen Receptor T Cells With Modified Interleukin-13 Preferentially Recognize IL13Rα2 and Suppress Malignant Glioma: A Preclinical Study. [2021]
Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. [2023]
Receptor for interleukin 13 is abundantly and specifically over-expressed in patients with glioblastoma multiforme. [2020]
Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells. [2021]
Checkpoint Blockade Reverses Anergy in IL-13Rα2 Humanized scFv-Based CAR T Cells to Treat Murine and Canine Gliomas. [2020]
Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells. [2022]
T cells redirected to interleukin-13Rα2 with interleukin-13 mutein--chimeric antigen receptors have anti-glioma activity but also recognize interleukin-13Rα1. [2021]
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