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Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

36 Participants Needed

B7-H3-CAR T Cells for Brain Tumor

Overseen ByJean Laboe, MSN, RN

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Must be taking: Anti-seizure medication

Must not be taking: Live vaccines

Disqualifiers: Immunodeficiency, HIV, Severe infections, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors.Primary objectives* To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).Secondary objectives* To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).* To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).

Will I have to stop taking my current medications?

Yes, you will need to stop certain medications before joining the trial. Chemotherapy and biologic therapy must be stopped at least 7 days before enrollment, and antibody therapy must be stopped for at least 3 half-lives or 30 days, whichever is shorter. Corticosteroids must be stable or decreasing for at least 1 week before enrollment, with a maximum dose specified.

Is B7-H3-CAR T cell therapy safe for humans?

Research on B7-H3-CAR T cells, also known as Anti-B7-H3 CAR T cells or Anti-CD276 CAR T cells, has shown promising results in targeting brain tumors and other solid cancers in preclinical studies. These studies suggest that the therapy can be effective with reduced levels of inflammatory responses when administered directly to the tumor site, but more research is needed to fully understand its safety in humans.¹ ² ³ ⁴ ⁵

What makes B7-H3-CAR T cell treatment unique for brain tumors?

B7-H3-CAR T cell treatment is unique because it targets the B7-H3 protein, which is commonly found on brain tumors but not on healthy tissues, allowing for a more precise attack on cancer cells. This approach is novel as it uses the body's own immune cells, modified to recognize and destroy tumor cells, offering a potential new option for patients with few existing treatments.¹ ³ ⁴ ⁵ ⁶

What data supports the effectiveness of the B7-H3-CAR T cell treatment for brain tumors?

Research shows that B7-H3-CAR T cells have shown promising results in preclinical studies for treating various brain tumors, including glioblastoma and neuroblastoma, by targeting the B7-H3 protein, which is often found in high levels on these tumors. These studies have demonstrated that B7-H3-CAR T cells can effectively attack tumor cells and improve survival in animal models.¹ ³ ⁴ ⁵ ⁶

Who Is on the Research Team?

Kelsey Bertrand

Principal Investigator

St. Jude Children's Research Hospital

Giedre Krenciute, PhD

Principal Investigator

St. Jude Children's Research Hospital

Christopher DeRenzo, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

The Loc3CAR trial is for children and young adults up to 21 years old with primary brain tumors. Participants must have measurable disease, a life expectancy over 8 weeks, and be able to perform daily activities at least half of the time (Karnofsky/Lansky score ≥50). They should not have severe infections or immune deficiencies, non-programmable ventricular shunts, or any condition that could affect study results.

Inclusion Criteria

My brain tumor is B7-H3 positive, H3K27-altered, or a typical DIPG.

Screening Eligibility: For Cohort B, must meet one of the following criteria: Adequate tumor tissue for central pathology review, Brainstem high-grade neoplasm with available imaging for central review, Life expectancy of > 12 weeks, Adult patient, parent, or legal guardian can understand and sign a written informed consent document

Procurement and T-cell Production Eligibility: Estimated life expectancy of >12 weeks

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Exclusion Criteria

Screening Eligibility: Clinically significant medical disorders compromising ability to tolerate protocol therapy or interfere with study procedure

Procurement and T-cell Production Eligibility: Participant has a non-programmable ventricular shunt, Known primary immunodeficiency or acquired immunodeficiency, Known HIV positivity, Severe intercurrent bacterial, viral, or fungal infection, Rapidly progressive disease, Known underlying medical condition not in the best interest of the participant, Unwilling or unable to provide consent for a 15-year long-term follow-up study

Treatment Eligibility: Participant has a non-programmable ventricular shunt, Known primary immunodeficiency or acquired immunodeficiency, Known HIV positivity, Severe intercurrent bacterial, viral, or fungal infection, Cardiovascular conditions within 6 months prior to study entry, Receiving therapy during the 'wash-out' period, Rapidly progressing disease, Received live vaccines within 30 days, Known underlying medical condition not in the best interest of the participant, Unwilling or unable to provide consent for a 15-year long-term follow-up study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive four B7-H3-CAR T cell infusions over a 4 week period via a CNS reservoir catheter

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Long-term follow-up

Participants continue follow-up on an institutional protocol to complete 15 years post-infusion

15 years

What Are the Treatments Tested in This Trial?

Interventions

B7-H3-CAR T cells

Trial Overview This Phase I trial tests B7-H3-CAR T cells delivered directly into the central nervous system via a catheter in patients with two types of brain tumors: relapsed/refractory non-brainstem tumors (Cohort A) and high-grade brainstem neoplasms (Cohort B). The goal is to determine the highest safe dose through six infusions over eight weeks.

How Is the Trial Designed?

2Treatment groups

Experimental Treatment

Group I: Arm B (diffuse midline gliomas [DMG])Experimental Treatment1 Intervention

Patients with DMG.

Group II: Arm A (relapsed/refractory CNS tumors)Experimental Treatment1 Intervention

Patients with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors.

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Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

B7-H3 CAR T cells have shown significant antitumor activity in various pediatric solid tumor models, including osteosarcoma and medulloblastoma, indicating their potential as a treatment option for relapsed pediatric malignancies.

The effectiveness of B7-H3 CAR T cells is linked to the density of the B7-H3 antigen on tumor cells, suggesting that this therapy could be selectively effective against tumors with high antigen expression while minimizing effects on normal tissues with lower expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors.Majzner, RG., Theruvath, JL., Nellan, A., et al.[2021]

B7-H3 is a promising target for immunotherapy in treating various brain cancers, as it helps create a tumor-friendly environment that allows cancer cells to grow and resist treatment.

Preclinical studies and early-phase trials have shown that targeting B7-H3 can lead to effective anti-tumor responses with manageable toxicity, and ongoing clinical trials are exploring its use in combination therapies for difficult-to-treat brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3 in Brain Malignancies: Immunology and Immunotherapy.Guo, X., Chang, M., Wang, Y., et al.[2023]

B7-H3 is a promising target for cancer immunotherapy due to its consistent expression in tumors and limited presence in healthy tissues, making it a suitable candidate for CAR-T therapy.

A newly developed anti-B7-H3 CAR-T demonstrated strong anti-tumor activity in vitro and showed sustained proliferation in response to repeated antigen challenges, indicating its potential effectiveness in treating resistant neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel anti-B7-H3 chimeric antigen receptor from a single-chain antibody library for immunotherapy of solid cancers.Birley, K., Leboreiro-Babe, C., Rota, EM., et al.[2022]