CART-EGFR-IL13Ra2 for Glioblastoma

Overseen By Stephen Bagley, MD, MSCE

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Bevacizumab, Temozolomide, others

Disqualifiers: Hepatitis, Cardiovascular disability, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cell therapy for individuals with glioblastoma, a specific type of brain cancer. The treatment uses modified T cells, a type of immune cell, to target and attack cancer cells. Participants must have a recently diagnosed glioblastoma with certain genetic traits and must have already undergone surgery and radiation. The trial aims to assess the safety and effectiveness of this treatment against the cancer. As a Phase 1 trial, the research focuses on understanding how the treatment functions in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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

The trial does not specify if you need to stop taking your current medications. However, it excludes participants who are on certain treatments like bevacizumab or temozolomide for their glioblastoma. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that CART-EGFR-IL13Ra2 cells are likely to be safe for humans?

Research has shown that CART-EGFR-IL13Ra2 cells appear safe for humans. In earlier studies, researchers introduced these cells into the brain to target specific cancer markers, and the results were promising. The treatment showed no serious side effects.

Another study also delivered the cells directly into the brain, with no reports of severe brain-related side effects. Patients tolerated the treatment well, suggesting it might be a safe option for those with glioblastoma.

However, as this is an early-stage trial, researchers are still confirming the treatment's safety. These studies aim to ensure safety before proceeding to larger trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for glioblastoma, which often involve surgery, radiation, and chemotherapy, CART-EGFR-IL13Ra2 cells offer a novel approach using specially engineered immune cells. This treatment is a type of CAR-T cell therapy, where patients' T-cells are modified to better recognize and attack glioblastoma cells by targeting specific proteins like EGFR and IL13Ra2. Additionally, this therapy is administered directly into the brain's ventricle system through an intracerebroventricular injection, allowing for precise delivery to the tumor site. Researchers are excited about this treatment because it represents a promising step forward in targeting cancer cells more effectively and with potentially fewer side effects than traditional therapies.

What evidence suggests that CART-EGFR-IL13Ra2 cells might be an effective treatment for glioblastoma?

Research has shown that a new treatment using special cells called CART-EGFR-IL13Ra2 holds promise for treating glioblastoma, a type of brain cancer. In this trial, participants will receive different doses of these cells. Studies have found that these cells can shrink tumors quickly, sometimes within just 48 hours. In half of the patients, the tumor size was reduced by at least 30%. Additionally, 75% of patients had their disease remain stable for at least two months. These CAR-T cells are designed to target two specific proteins often found in tumor cells, which helps them effectively locate and attack the cancer. Early results suggest that this treatment is not only active but also safe for patients. ^{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?

Adults over 18 with newly diagnosed, EGFR-amplified, MGMT-unmethylated glioblastoma who've had maximal tumor resection can join. They must have completed radiotherapy without disease progression and be in good enough health to perform daily activities (Karnofsky Performance Status ≥ 60%).

Inclusion Criteria

I am at the first step of the process.

My glioblastoma is new, has EGFR amplification, is MGMT unmethylated, and IDH wildtype with specific tumor features.

I've had surgery to remove as much of my tumor as safely possible.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy

Participants complete a course of radiotherapy (60 Gy) without temozolomide as per their routine cancer care

6 weeks

Treatment

Participants receive a single fixed dose of CART-EGFR-IL13Ra2 cells via intracerebroventricular delivery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• CART-EGFR-IL13Ra2 cells

Trial Overview The trial is testing a new therapy using the patient's own T cells modified to target specific cancer cell markers (CART-EGFR-IL13Ra2 cells) after initial radiotherapy. It aims to evaluate safety, how the body processes it, and its preliminary effectiveness.

How Is the Trial Designed?

Group I: Dose Level 1 Experimental Treatment 1 Intervention

Dose Level 1 (DL1): will receive single fixed dose of 2.5x10\^7 CART-EGFR-IL13Ra2 cells via intracerebroventricular (ICV) injection on Day 0.

Group II: Dose Level -1 (DL-1) Experimental Treatment 1 Intervention

Dose Level-1 (DL-1): will receive single fixed dose of 1x10\^7 CART-EGFR-IL13Ra2 cells via intracerebroventricular (ICV) injection on Day 0. This dose level will only be explored if there are at least two TLTs observed at DL1.

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. 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 ...

5. 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 ...

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 ...