CAR T Cell Therapy for Pediatric Solid Cancers

Overseen By Katie Albert, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Seattle Children's Hospital

Must not be taking: Anti-cancer agents, Chemotherapy

Disqualifiers: Active malignancy, CNS pathology, Severe infection, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for young people with solid tumors that have returned or don't respond to other treatments. It uses modified T cells, a type of immune cell, from the participant’s own blood to target and kill cancer cells. Participants are divided into two groups: one receives T cells targeting a marker called EGFR, while the other receives T cells targeting both EGFR and another marker, CD19, to determine which is more effective. This trial suits children and young adults with non-CNS solid tumors expressing EGFR who have struggled with standard treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anti-cancer agents or chemotherapy before enrolling. If you have been on certain therapies, there are specific waiting periods before you can join the trial, such as 7 days after the last chemotherapy or biologic therapy, and 30 days after the last dose of anti-tumor antibody therapy.

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

Research has shown that EGFR806 CAR T cell therapy is generally safe for children and young adults with hard-to-treat solid tumors. Studies have found that this treatment has an acceptable level of side effects, meaning it doesn't cause harmful reactions for most patients. Some patients even experienced a decrease in tumor size.

The treatment uses a special type of immune cell, called a T cell, taken from the patient's blood and modified to attack specific cancer cells. For those receiving the combination treatment, the therapy also targets cells that help strengthen the immune response.

While side effects can occur, they are usually manageable. For example, a common reaction is cytokine release syndrome, an overreaction by the immune system, but doctors can treat it. If any serious problems arise, there are ways to safely remove the modified cells from the body.

In summary, early findings suggest that EGFR806 CAR T cell therapy is well-tolerated, but as with any new treatment, careful monitoring is essential to ensure patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about EGFR806 CAR T cell therapy because it offers a novel approach for treating pediatric solid cancers. Unlike traditional treatments like chemotherapy and radiation, which indiscriminately attack both healthy and cancerous cells, EGFR806 CAR T cells are engineered to specifically target and attack cancer cells displaying the EGFR806 marker. This precision reduces damage to healthy cells and potentially leads to fewer side effects. Additionally, the inclusion of CD19CAR(2G)-T2A-HER2tG in one of the treatment arms targets multiple cancer markers simultaneously, which could enhance effectiveness against tumors that express these proteins.

What evidence suggests that this trial's treatments could be effective for pediatric solid cancers?

Research has shown that EGFR806 CAR T cells could be promising for treating solid tumors in children. These specially modified cells are generally safe and can target and attack tumor cells with the EGFR protein. In this trial, one group of participants will receive EGFR806 CAR T cells alone, which have, in some cases, helped shrink tumors. Another group will receive a combination of EGFR806 CAR T cells and CD19 CAR T cells. This combination aims to enhance the effectiveness and longevity of the EGFR-targeted cells, potentially strengthening the body's ability to fight cancer, as CD19 helps the immune system recognize and attack cancer cells more effectively. Early results suggest this method could provide a new option for children and young adults with hard-to-treat cancers. ^{1 2 5 6 7}

Who Is on the Research Team?

Katie Albert, MD

Principal Investigator

Seattle Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1-30 with certain non-CNS solid tumors that are recurrent or resistant to treatment. Participants must have a life expectancy of at least 8 weeks, be able to undergo apheresis (a procedure to collect immune cells), and not have had recent myeloablative therapy unless they've recovered. They should not be receiving other cancer treatments or have active infections, CNS pathology, GVHD, primary immunodeficiency, or be pregnant.

Inclusion Criteria

I am between 15 and 30 years old.

It's been over 6 weeks since my last intense therapy and stem cell transplant.

Patients of childbearing potential must agree to use highly effective contraception

Exclusion Criteria

Pregnant or breastfeeding

Unwilling to provide consent/assent for participation in the study and 15 year follow up period

I have a current brain or spinal cord condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of genetically modified T cells (CD4 and CD8) targeting EGFR and potentially CD19

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety, efficacy, and persistence of CAR T cells in the blood and bone marrow

12 weeks

Multiple visits (in-person)

Long-term follow-up

Participants are monitored for long-term safety and efficacy, including anti-tumor responses and survival characteristics

84 days

What Are the Treatments Tested in This Trial?

Interventions

• EGFR806 CAR T Cell Immunotherapy

Trial Overview The study tests genetically modified T cells designed to target EGFR on tumors in two groups: one receives CAR T cells targeting only EGFR; the other targets both EGFR and CD19. The goal is to see if these T cells are safe, can be made successfully from participants' blood, what dose is tolerated best without severe side effects (except manageable ones like cytokine release syndrome), how long they last in the body, and their effectiveness against tumors.

How Is the Trial Designed?

Group I: EGFR806CAR(2G)-EGFRt and CD19CAR(2G)-T2A-HER2tG Experimental Treatment 1 Intervention

Autologous CD4+ and CD8+ T cells that have been genetically modified to express the EGFR806CAR(2G)-EGFRt and CD19CAR(2G)-T2A-HER2tG

Group II: EGFR 806CAR(2G) -EGFRt Experimental Treatment 1 Intervention

Autologous CD4+ and CD8+ T cells that have been genetically modified to express the EGFR 806CAR(2G) -EGFRt

EGFR806 CAR T Cell Immunotherapy is already approved in United States for the following indications:

Approved in United States as EGFR806 CAR T Cell Immunotherapy for:

• Recurrent/Refractory Solid Tumors in Children and Young Adults

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Published Research Related to This Trial

CAR T-cell immunotherapy, which involves genetically modifying T cells to target cancer cells, has shown promising results, especially in treating B-cell malignancies with several patients achieving complete and durable responses.

Current research is expanding CAR T-cell therapy to solid tumors, specifically targeting members of the ErbB family, indicating a potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ErbB-targeted CAR T-cell immunotherapy of cancer. Whilding, LM., Maher, J.[2022]

In a phase I clinical study involving 11 patients with EGFR-positive relapsed/refractory non-small cell lung cancer (NSCLC), EGFR-targeted CAR-T cell therapy was found to be safe and well-tolerated, with no severe toxicities reported.

Out of the evaluable patients, 2 achieved a partial response and 5 had stable disease for 2 to 8 months, indicating that this therapy can effectively target and potentially eradicate EGFR-positive tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer. Feng, K., Guo, Y., Dai, H., et al.[2022]

CAR-T cell therapy, while currently approved only for B cell malignancies, shows promising potential for treating pediatric brain tumors, with early clinical trials indicating some positive responses.

Recent preclinical studies have identified new tumor antigens and combination strategies that enhance the effectiveness of CAR-T cells, particularly when administered directly to the tumor site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cells for pediatric brain tumors: Present and future. Leruste, A., Beccaria, K., Doz, F.[2021]

Brain tumors are the most common solid tumors in children and the leading cause of cancer-related deaths, highlighting the urgent need for more effective treatments.

Recent advancements in CAR T cell immunotherapy show promise for improving outcomes in pediatric brain cancer, with ongoing research focusing on specific targets and strategies to enhance the effectiveness of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in CAR T cell immunotherapy for paediatric brain tumours. Rao, P., Furst, L., Meyran, D., et al.[2022]

The EGFR806-CAR T cells were designed to specifically target tumor cells expressing low levels of EGFR, showing effective cytokine secretion and glioma cell destruction in vitro, while sparing normal brain cells, indicating a safer therapeutic profile.

In vivo studies demonstrated that EGFR806-CAR T cells could successfully treat glioma in mice, with 50% survival at 90 days and complete tumor eradication with additional IL-2 support, showcasing their potential efficacy in solid tumor therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EGFR806-CAR T cells selectively target a tumor-restricted EGFR epitope in glioblastoma. Ravanpay, AC., Gust, J., Johnson, AJ., et al.[2020]

The engineered FR806 receptor allows for the selective targeting and elimination of T cells that have been modified for therapy, minimizing damage to normal tissues, which is crucial for safety in adoptive T cell therapies.

In experiments with immuno-compromised mice, the antibody-drug conjugate CH12-MMAF effectively eliminated most of the FR806-expressing T cells, demonstrating the efficacy of this safety switch in controlling T cell populations post-therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Fusion Receptor as a Safety Switch, Detection, and Purification Biomarker for Adoptive Transferred T Cells. Wu, X., Shi, B., Zhang, J., et al.[2018]

Chimeric antigen receptor (CAR) T cell therapy has shown robust efficacy in treating pediatric B cell acute lymphocytic leukemia (ALL), providing a potential cure for children with this previously lethal disease.

Pediatric cancers are particularly suitable for immune-based therapies due to their unique developmental origins and the expression of specific cell surface molecules, although challenges remain in developing effective immunotherapeutics for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Based Approaches for the Treatment of Pediatric Malignancies. Bosse, KR., Majzner, RG., Mackall, CL., et al.[2021]

CAR T cell therapy shows promise for treating pediatric sarcomas, with early trials indicating positive outcomes for some patients, despite challenges in effectiveness due to the immunosuppressive tumor microenvironment.

Current clinical trials are exploring CAR T cells targeting various tumor antigens like HER2 and GD2, and new strategies are being developed to enhance the efficacy of these therapies against the immunosuppressive effects of the tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma. Terry, RL., Meyran, D., Fleuren, EDG., et al.[2021]

ABT-806, a monoclonal antibody targeting activated EGFR, was found to have a favorable safety profile in a phase I study involving 49 patients with advanced solid tumors, with only one dose-limiting toxicity reported and common side effects being low-grade.

The recommended phase two dose (RP2D) was established at 24 mg/kg, and while no objective tumor responses were observed, some patients experienced prolonged stable disease, indicating potential for further investigation in EGFR-amplified tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of ABT-806 in subjects with advanced solid tumors. Cleary, JM., Reardon, DA., Azad, N., et al.[2018]

CAR-T cell therapy has shown effective tumor-killing activity in treating B cell-derived hematological tumors and is being explored for solid tumors, indicating its potential as a versatile cancer treatment.

However, the therapy can lead to serious and potentially life-threatening adverse events, highlighting the need for careful monitoring and management strategies in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse events and coping strategies of CAR-T cells in the treatment of malignant tumors. Chen, X., Li, P., Tian, B., et al.[2023]

The chimeric antibody mAb 806 (ch806) specifically targets tumor cells with overexpressed or mutant forms of the epidermal growth factor receptor (EGFR), showing excellent tumor site targeting in patients without affecting normal tissues.

In clinical studies, ch806 demonstrated no significant toxicity, highlighting its potential as a safe and effective treatment option for various cancers compared to other EGFR-targeting antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors. Scott, AM., Lee, FT., Tebbutt, N., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03618381

Study Details | NCT03618381 | EGFR806 CAR T Cell ... This is a phase I, open-label, non-randomized study that will enroll pediatric and young adult research participants with relapsed or refractory non-CNS ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.2541

STRIvE-01: Phase I study of EGFR806 CAR T-cell ... EGFR806 directed CAR-T cells have an acceptable toxicity profile in CYA with R/RST and demonstrate anti-tumor activity in some patients.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6925027/

EGFR806-CAR T cells selectively target a tumor-restricted ... We found that cytokine release and target cell killing by the EGFR806-CAR were similarly effective in all glioblastoma cell lines tested, and ...

4. trial.medpath.com trial.medpath.com/clinical-trial/57c92c53fbdd977e/egfr806-car-t-cell-immunotherapy-solid-tumors

EGFR806 CAR T Cell Immunotherapy for Recurrent ... This is a phase I, open-label, non-randomized study that will enroll pediatric and young adult research participants with relapsed or ...

5. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.2022.40.16_suppl.2541

Phase I study of EGFR806 CAR T-cell immunotherapy for ... Published data and EGFR immunohistochemistry (IHC) performed on tissue microarrays in- dicate that 15-40% of pediatric solid tumors (ST) express EGFR. The ...

6. seattlechildrens.org seattlechildrens.org/research/research-studies-clinical-trials/current-studies/strive-01/

STRIvE-01: Phase I Study of EGFR806 CAR T Cell ... Is T-cell therapy safe to give to children and young adults with relapsed or refractory solid tumors? What is the best dose of CAR T cells for children and ...

7. clinicaltrial.be clinicaltrial.be/en/details/67764?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

EGFR806 CAR T Cell Immunotherapy for Recurrent ... This is a phase I, open-label, non-randomized study that will enroll pediatric and young adult research participants with relapsed or refractory ...