CART-EGFR-IL13Ra2 for Glioblastoma

Overseen By University of Pennsylvania

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Bevacizumab, Immunosuppressants

Disqualifiers: Hepatitis, Cardiovascular disability, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CART-EGFR-IL13Ra2, a type of cell therapy, for individuals with glioblastoma, an aggressive brain cancer that has recurred after radiation therapy. The study aims to determine the safety and effectiveness of this treatment and how the body processes it. The treatment will be administered in three different ways, with some participants receiving a single dose and others receiving repeated doses. Suitable candidates for this trial have glioblastoma that has returned after previous treatment and have undergone specific genetic testing on their tumor. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on bevacizumab, you must not have taken it within 3 months before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CART-EGFR-IL13Ra2, a treatment for glioblastoma, has promising safety results in early studies. These studies found that patients generally tolerated the treatment well, with no serious nerve damage reported. Patients experienced a reduction in tumor size without major side effects. This suggests the treatment is relatively safe for humans, although further research is needed to confirm its long-term safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for glioblastoma, such as surgery, radiation, and chemotherapy, CART-EGFR-IL13Ra2 uses a cutting-edge approach called CAR T-cell therapy. This treatment involves reprogramming a patient's own immune cells to better recognize and attack cancer cells, specifically targeting the EGFR and IL13Ra2 proteins found on glioblastoma cells. Researchers are excited because this method could offer a more precise attack on the tumor, potentially leading to better outcomes with fewer side effects compared to conventional therapies. Additionally, the trial includes innovative dosing strategies, such as repeated doses and single doses given pre-operatively, which could further enhance the treatment’s effectiveness.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

Research has shown that a new treatment using CART-EGFR-IL13Ra2 cells may help treat glioblastoma, a type of brain cancer. In earlier studies, this treatment quickly shrank tumors, sometimes within just 48 hours. About half of the patients experienced a tumor reduction of at least 30%, and 75% had stable disease for at least two months. This trial will evaluate different administration methods of CART-EGFR-IL13Ra2: some participants will receive a single fixed dose following lymphodepletion, others will receive repeated doses, and another group will receive a single fixed dose in the pre-operative setting. This treatment targets specific proteins on cancer cells, allowing for a focused attack on the tumor. Early evidence suggests this method is both safe and potentially effective for patients with recurring glioblastoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Stephen Bagley, MD, MSCE

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for individuals with glioblastoma that has come back after radiotherapy. Participants must have EGFR-amplified tumors, which means their cancer cells have too many copies of a gene called EGFR.

Inclusion Criteria

Signed, written informed consent

Subjects of reproductive potential must agree to use acceptable birth control methods

I am 18 years old or older.

Exclusion Criteria

Severe, active co-morbidity that would preclude participation in the study

Patients who are pregnant or nursing

History of allergy or hypersensitivity to study product excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to CART-EGFR-IL13Ra2 cell administration

1-2 weeks

Treatment

Participants receive CART-EGFR-IL13Ra2 cells, either as a single fixed-dose or repeated doses, depending on the arm

Up to 28 days

Follow-up

Participants are monitored for safety, efficacy, and adverse events

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• CART-EGFR-IL13Ra2

Trial Overview The study is testing different doses of CART-EGFR-IL13Ra2 T cells, which are immune cells modified to target and kill glioblastoma tumor cells. It's an early-phase trial to check safety, how well it works, and how the body processes these special T cells.

How Is the Trial Designed?

Group I: Arm B Active Control 1 Intervention

Subjects will receive repeated dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion.

Group II: Arm C Active Control 1 Intervention

Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 in the pre-operative setting.

Group III: Arm A Active Control 1 Intervention

Subjects will receive a single fixed-dose administration of CART-EGFR-IL13Ra2 cells following lymphodepletion.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38480922/

Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 ... Taken together, these first-in-human data demonstrate the preliminary safety and bioactivity of CART-EGFR-IL13Rα2 cells in rGBM. An encouraging ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.102

A phase 1 study of intracerebroventricular (ICV) delivery ... Conclusions: ICV delivery of CART-EGFR-IL13Rα2 is feasible and appears safe. CART-EGFR-IL13Rα2 cells are bioactive and exhibit an encouraging ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05168423

Study Details | NCT05168423 | CART-EGFR-IL13Ra2 in ... 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 ...

4. healio.com healio.com/news/hematology-oncology/20240327/we-were-shocked-cart-rapidly-reduces-size-of-brain-tumors-in-phase-1-trial

CAR-T rapidly reduces size of brain tumors in phase 1 trial Novel CAR-T targeting both EGFR and IL13Ra2 reduced tumor sizes within 48 hours in patients with glioblastoma. No grade 4 or 5 neurotoxicity ...

5. nature.com nature.com/articles/s41698-024-00753-0

CAR-T cell therapy for the treatment of adult high-grade ... In this trial, half of the patients showed at least 30% tumor shrinkage and 75% of patients showed stable disease at least 2 months after CAR-T ...

6. trials.braintumor.org trials.braintumor.org/trials/NCT06973096

CART-EGFR-IL13Ra2 in Newly Diagnosed GBM Following ... 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 ...