B7-H3 CAR T Cells for Brain Cancer

Not yet recruiting at 1 trial location

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Robbie Majzner

Must not be taking: Systemic corticosteroids, Anti-cancer drugs

Disqualifiers: Bulky tumor, Brain herniation, Immunodeficiency, others

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

Compensation: Varies

Number of Visits: 14

Duration: 8 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy, B7-H3 CAR T cells, to determine its safety and effectiveness for children and young adults with recurrent or worsening brain tumors. The therapy targets a protein on many tumor cells, aiming to attack the cancer directly. Participants will also receive the chemotherapy drugs Fludarabine and Cyclophosphamide to prepare their bodies for the treatment. Suitable candidates have a recurrent brain tumor, such as medulloblastoma or ependymoma, and have previously tried standard treatments. 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 innovative therapy.

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

Research has shown that B7-H3 CAR T cells have a promising safety record in early studies. For instance, research on recurring glioblastoma found this therapy to be safe and well-tolerated, with no serious side effects preventing dose escalation. Another study demonstrated that B7-H3 CAR T cells were safe for children with a brain tumor called DIPG. These children received the treatment directly into the brain, and it was well-tolerated even at higher doses.

The trial also includes two other treatments: Fludarabine and Cyclophosphamide, which are types of chemotherapy. While these drugs are commonly used in cancer treatments, they can cause side effects like lowering blood cell counts, increasing the risk of infection. Overall, evidence suggests that B7-H3 CAR T cell therapy is generally safe, but participating in any clinical trial carries some risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for brain cancer, like surgery, radiation, and chemotherapy, aim to remove or kill cancer cells but often come with significant side effects and can miss some cancerous cells. B7-H3.CD28Z.CART is unique because it uses genetically modified T cells that are designed to specifically target and attack cancer cells expressing the B7-H3 protein. This approach is promising because it leverages the body's own immune system and has the potential for more precise targeting of cancer cells, potentially leading to better outcomes and fewer side effects. Researchers are excited because this method could provide a more effective and less invasive treatment option for brain cancer patients, especially those who have limited options with existing therapies.

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

Research has shown that B7-H3 CAR T cells could be a promising treatment for brain tumors. Studies have found that many brain tumor cells often have large amounts of B7-H3, making it an ideal target for this therapy. In lab tests, B7-H3 CAR T cells demonstrated strong activity against brain tumors, such as gliomas and ependymomas, by effectively killing the cancer cells. These cells also grow and persist in the body, which is crucial for ongoing treatment. Early findings suggest that B7-H3 CAR T cell therapy is safe and manageable for patients with brain tumors, with no severe side effects reported in initial studies. Participants in this trial will enroll in different arms to evaluate the dose escalation and expansion of B7-H3 CAR T cells in both standard and high-risk strata. ^{2 3 6 7 8}

Who Is on the Research Team?

Susan Chi

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for children and young adults with recurrent or progressive brain tumors, including various specific types such as Rhabdoid Tumor and Medulloblastoma. Participants must have a tumor that has returned after treatment or is advancing despite therapy.

Inclusion Criteria

I've had standard treatment and recovered from its side effects.

Participants must have adequate pre-trial tumor material available to determine B7-H3 expression status

Participants must have a life expectancy of greater than 12 weeks

Exclusion Criteria

My tumor is not considered bulky.

I do not have any severe, uncontrolled infections.

Participants with clinical or radiological evidence of brain herniation are ineligible

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive Fludarabine and Cyclophosphamide to prepare the body for cell therapy

3 days

3 visits (in-person)

Treatment

Participants receive B7-H3 CAR T cell infusion and subsequent intracerebroventricular infusions every 28 days

8 months

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Follow-up every 3 months

Long-term Follow-up

Annual follow-up to monitor long-term safety and survival

13 years

Annual visits

What Are the Treatments Tested in This Trial?

Interventions

• B7-H3.CD28Z.CART

Trial Overview

The study tests the safety and effectiveness of B7-H3 CAR T cells at different doses, combined with chemotherapy drugs Fludarabine and Cyclophosphamide, in treating recurrent or progressive brain tumors in the pediatric and young adult population.

How Is the Trial Designed?

Group I: Dose Expansion for B7-H3.CD28Z.CART in Standard Risk Stratum Experimental Treatment 3 Interventions

Dose expansion will occur per dose-limiting toxicity rules. * Baseline visit * Apheresis to obtain T cells * Days -4, -3, -2: predetermined doses of Fludarabine and Cyclophosphamide 1x daily * Day 0: B7-H3 CAR T cell infusion 1x daily * 2 doses of B7-H3 CAR T cell infusion Intracerebroventricular (ICV) Infusion every 28 days until 8 doses total according to clinical response * Follow up every 3 months after last infusion up until 2 years * Long term follow annually for an additional 13 years

Group II: Dose Expansion for B7-H3.CD28Z.CART in High Risk Stratum Experimental Treatment 3 Interventions

Dose expansion will occur per dose-limiting toxicity rules. * Baseline visit * Apheresis to obtain T cells * Days -4, -3, -2: predetermined doses of Fludarabine and Cyclophosphamide 1x daily * Day 0: B7-H3 CAR T cell infusion 1x daily * 2 doses of B7-H3 CAR T cell infusion Intracerebroventricular (ICV) Infusion every 28 days until 8 doses total according to clinical response * Follow up every 3 months after last infusion up until 2 years * Long term follow annually for an additional 13 years

Group III: Dose Escalation for B7-H3.CD28Z.CART in Standard Risk Stratum Experimental Treatment 3 Interventions

Participants will be enrolled in a staggered, sequential fashion using a modified 3 + 3 dose escalation design, assigning participants to one of three intravenous dose levels to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of IV B7-H3.CD28Z.CART. Dose escalation will occur per dose-limiting toxicity rules. * Baseline visit * Apheresis to obtain T cells * Days -4, -3, -2: predetermined doses of Fludarabine and Cyclophosphamide 1x daily * Day 0: B7-H3 CAR T cell infusion 1x daily * 2 doses of B7-H3 CAR T cell infusion Intracerebroventricular (ICV) Infusion every 28 days until 8 doses total according to clinical response * Follow up every 3 months after last infusion up until 2 years * Long term follow annually for an additional 13 years

Group IV: Dose Escalation for B7-H3.CD28Z.CART in High Risk Stratum Experimental Treatment 3 Interventions

Participants will be enrolled in a staggered, sequential fashion using a modified 3 + 3 dose escalation design, assigning participants to one of three intravenous dose levels to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of IV B7-H3.CD28Z.CART. Dose escalation will occur per dose-limiting toxicity rules. * Baseline visit * Apheresis to obtain T cells * Days -4, -3, -2: predetermined doses of Fludarabine and Cyclophosphamide 1x daily * Day 0: B7-H3 CAR T cell infusion 1x daily * 2 doses of B7-H3 CAR T cell infusion Intracerebroventricular (ICV) Infusion every 28 days until 8 doses total according to clinical response * Follow up every 3 months after last infusion up until 2 years * Long term follow annually for an additional 13 years

Who Is Running the Clinical Trial?

Robbie Majzner

Lead Sponsor

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6713854/

B7-H3 as a Novel CAR-T Therapeutic Target for ...

Our results suggested that B7-H3 may serve as a promising therapeutic target for CAR-T therapy against GBM. Result. B7-H3 Expression Level among Glioma and the ...

2.

onclive.com

onclive.com/view/b7-h3-directed-car-t-cell-therapy-has-acceptable-safety-profile-in-recurrent-glioblastoma

B7-H3–Directed CAR T-Cell Therapy Has Acceptable ...

B7-H3–directed CAR T-cell therapy showed safety and tolerability in recurrent glioblastoma, with no dose-limiting toxicities reported in the ...

3.

techfinder.stanford.edu

techfinder.stanford.edu/technology/treatment-gliomas-anti-b7h3-car-t-cells

Treatment of Gliomas with Anti-B7H3 CAR-T Cells - Stanford

CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. Cinical Cancer ...

4.

aacrjournals.org

aacrjournals.org/clincancerres/article/31/17/3754/764197/B7-H3-CAR-T-Cells-Are-Effective-against

B7-H3 CAR T Cells Are Effective against Ependymomas but ...

In vitro, human B7-H3.CAR T cells had potent anti-ependymoma cytolytic activity, expansion, and persistence, which was inversely correlated with the ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05366179

NCT05366179 | Autologous CAR-T Cells Targeting B7-H3 ...

The purpose of this study is to test the safety of using T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (CAR.B7-H3T cells) in ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07358260

NCT07358260 | B7-H3.CD28Z.CART in Solid Tumors

This is a Phase I, open-label, single-center, dose-escalation study testing the safety and effectiveness of a new cell therapy B7-H3.CD28Z.CART ...

7.

aacrjournals.org

aacrjournals.org/cdnews/news/2074/BrainChild-03-Trial-Supports-Safety-of-B7-H3-CAR-T

BrainChild-03 Trial Supports Safety of B7-H3 CAR T-cell ...

Main Finding: A phase I trial supported the safety and feasibility of repeated intracranial infusions of B7-H3 CAR T cells for DIPG.

8.

nature.com

nature.com/articles/s41591-024-03451-3

Intracerebroventricular B7-H3-targeting CAR T cells for ...

We show the safety of repetitive intracerebroventricularly (ICV) dosed B7-H3 CAR T cells up to 10 × 107 cells per dose to children with DIPG, ...