B7-H3CART for Solid Tumors

Overseen By Amy Li

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Other malignancy, Brain metastases, Infections, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 8

Duration: 1 day

41 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called B7-H3CART (B7-H3 Chimeric Antigen Receptor T Cells) for children and young adults with solid tumors unresponsive to other treatments. The goal is to determine its safety and feasibility for intravenous administration. Participants should have a solid tumor, such as neuroblastoma or osteosarcoma, that has recurred or resisted standard therapies. This trial may suit those who have exhausted usual treatments and seek new options. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

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

The trial protocol does not specify if you must stop all current medications. However, there is a required washout period of at least 2 weeks or 5 half-lives for prior systemic therapies, except for immune checkpoint therapies, which require 5 half-lives. Systemic corticosteroids or immunosuppressive therapies require a one-week washout. Please consult with the trial team for guidance on your specific medications.

Is there any evidence suggesting that B7-H3CART is likely to be safe for humans?

Research has shown that B7-H3CART cells are generally safe and well-tolerated. In one study, these cells targeted cancer cells without harming healthy tissues. Another study aimed to find the highest safe dose and suggested that B7-H3-CAR T cells are safe for patients with certain solid tumors. While these results are promising, it is important to remember that this treatment remains in the early testing stages, so more information is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

B7-H3CART is unique because it uses a novel approach to combat solid tumors by employing CAR T-cell technology, specifically targeting the B7-H3 protein found on cancer cells. Unlike traditional treatments like chemotherapy or radiation, which attack both cancerous and healthy cells, B7-H3CART is designed to distinguish and directly attack cancer cells, potentially reducing side effects. Researchers are excited about this treatment because it represents a targeted and personalized form of therapy, which could lead to more effective and less harmful cancer treatment options.

What evidence suggests that B7-H3CART might be an effective treatment for solid tumors?

Research has shown that B7-H3 CAR T cells, which participants in this trial will receive, can help fight certain types of cancer. One study found these cells very effective at killing cancer cells, leading to a noticeable reduction in tumor size over time. Another study discovered that B7-H3 CAR T cells stopped liver tumors from growing, with half of the cases showing complete tumor disappearance. Additionally, early lab studies demonstrated that these cells could successfully remove primary tumors and prevent their return. Overall, initial findings suggest that B7-H3 CAR T cells have promising effects against cancer, especially for those that are difficult to treat. ^{1 2 3 4 6}

Who Is on the Research Team?

Sneha Ramakrishna, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for children and young adults with solid tumors like sarcoma, neuroblastoma, or osteosarcoma that have come back or didn't respond to previous treatments. The tumors must express a target called B7-H3. Specific eligibility details are not provided but would typically include health status and prior therapies.

Inclusion Criteria

I am between 2 and 25 years old.

My cancer is incurable, has returned or worsened after all treatments.

Availability of evaluable or measurable disease during dose escalation/expansion

Exclusion Criteria

I have had serious heart problems in the last year.

Receiving any other current investigational agents

Severe immediate hypersensitivity reaction to study agents

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 for B7-H3CART cell infusion

1 week

Daily visits for 7 days

Treatment

Participants receive a single dose of intravenous B7-H3CART cells

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• B7-H3CART

Trial Overview The study is testing the safety of a new therapy where patients receive an IV dose of genetically engineered T cells (B7-H3CART) designed to attack cancer cells expressing B7-H3. It follows a '3+3' design which means small groups are given increasing doses to find the safest amount.

How Is the Trial Designed?

Group I: Lymphodepletion Experimental Treatment 1 Intervention

Fludarabine 30 mg/m2 per day IV for 4 days: 5, -4, 3, -2 Cyclophosphamide 500 mg/m2 per day IV for 3 days: -5, -4, -3 Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Crystal Mackall, MD

Lead Sponsor

Trials

6

Recruited

240+

Published Research Related to This Trial

B7-H3.CAR-T cells effectively controlled the growth of various cancers, including pancreatic ductal adenocarcinoma, ovarian cancer, and neuroblastoma, in both laboratory and mouse models, indicating their potential as a powerful immunotherapy.

The use of 4-1BB co-stimulation in B7-H3.CAR-T cells led to lower PD-1 expression and enhanced antitumor activity, suggesting a mechanism that could improve the effectiveness of these CAR-T therapies without causing significant toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Responses in the Absence of Toxicity in Solid Tumors by Targeting B7-H3 via Chimeric Antigen Receptor T Cells. Du, H., Hirabayashi, K., Ahn, S., et al.[2021]

B7-H3 is widely expressed in various human solid tumors but has limited expression in normal tissues, making it a promising target for CAR T-cell therapy.

Combining B7-H3.CAR T cells with the epigenetic drug SAHA significantly boosts their ability to kill solid cancer cells, suggesting this combination could improve treatment outcomes in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3-Specific CAR T Cells in Solid Tumors. Lei, X., Ou, Z., Yang, Z., et al.[2022]

Low-affinity CAR-T cells targeting the oncofetal antigen glypican 3 (GPC3) effectively kill tumor cells without causing toxicity to normal tissues, unlike high-affinity CAR-T cells that induce harmful side effects due to on-target, off-tumor binding.

An innovative approach using anti-TNF-α antibody therapy allows for the selective elimination of early activated CAR-T cells, helping to manage toxicity while maintaining tumor control, demonstrating a potential method to enhance the safety of CAR-T therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rational design of chimeric antigen receptor T cells against glypican 3 decouples toxicity from therapeutic efficacy. Giardino Torchia, ML., Gilbreth, R., Merlino, A., et al.[2022]

Chimeric antigen receptor T-cell therapy is a promising immunotherapy that shows effective results in treating cancers that have not responded to other treatments, as it uses genetically engineered T cells to target and destroy tumor cells.

There is a need for more information on the safety profile of this therapy, particularly regarding skin-related side effects, to improve early recognition and management of these adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous manifestations of chimeric antigen receptor T-cell therapy: An introduction for dermatologists. Nusbaum, KB., Dulmage, B., Choi, JN., et al.[2022]

B7-H3 is highly expressed in prostate cancer cells and tissues, making it a promising target for immunotherapy, particularly for developing CAR-T cell therapies.

The newly developed B7-H3 CAR-T cells effectively inhibited prostate cancer growth in both laboratory and animal models, demonstrating their potential for clinical application in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer. Li, S., Zhang, M., Wang, M., et al.[2023]

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 solid tumors due to its overexpression in tumors and limited presence in normal tissues, making it a suitable candidate for chimeric antigen receptor (CAR) therapies.

Initial trials of B7-H3-targeted CAR-T cell therapies have shown safety, but their effectiveness has been limited; strategies such as local delivery, enhancing CAR-T cell persistence, and combining with other treatments may improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3-targeted CAR-T cell therapy for solid tumors. Li, G., Wang, H., Wu, H., et al.[2022]

CAR-modified NK-92MI cells targeting the B7-H3 molecule showed significantly enhanced ability to kill B7-H3-positive tumor cells, indicating improved efficacy in cancer treatment.

In mouse models of non-small cell lung cancer, these engineered NK cells not only inhibited tumor growth but also extended the survival of the mice, supporting their potential use in adoptive cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting B7-H3 Immune Checkpoint With Chimeric Antigen Receptor-Engineered Natural Killer Cells Exhibits Potent Cytotoxicity Against Non-Small Cell Lung Cancer. Yang, S., Cao, B., Zhou, G., et al.[2020]

B7-H3 CAR-T cells, engineered to target a protein commonly found in solid tumors, demonstrated strong antitumor activity in both laboratory tests and mouse models, suggesting their potential effectiveness against advanced solid tumors.

The addition of PD-1 decoy receptors to these CAR-T cells enhanced their persistence and antitumor activity, indicating a promising strategy for improving CAR-T therapy outcomes in challenging solid tumor environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3 specific T cells with chimeric antigen receptor and decoy PD-1 receptors eradicate established solid human tumors in mouse models. Huang, B., Luo, L., Wang, J., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39255444/

STRIvE-02: A First-in-Human Phase I Study of Systemically ... Conclusion: B7-H3 CAR T cells are tolerable and demonstrate limited antitumor activity without acute on-target, off-tumor toxicity.

2. nature.com nature.com/articles/s41416-025-03114-1

The pronounced cytotoxic effects of chimeric antigen ... Our findings revealed that B7-H3 CAR-T cells effectively suppressed liver tumor growth (Fig. 4d, e), with a complete response rate of 50% (8/16 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04897321

Study Details | NCT04897321 | B7-H3-Specific Chimeric ... The study will evaluate the safety and maximum tolerated dose (MTD) of B7-H3-CAR T cells, using a standard 3+3 study design and a 6-week evaluation period. The ...

4. jitc.bmj.com jitc.bmj.com/content/13/1/e010083

Novel B7-H3 CAR T cells show potent antitumor effects in ... Our preclinical study demonstrates that these B7-H3-targeted CAR T cells effectively eliminated primary tumors and controlled rechallenge tumor ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0171298525000221

Development and evaluation of novel CAR-T Cell therapy The B7-H3-CAR-T cells effectively lysed these tumor cells, as evidenced by a significant decrease in the normalized cell index over time compared to NC-T cells ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2062

Safety and efficacy of B7-H3 targeting CAR-T cell therapy ... In this trial, treating rGBM with TX103 is deemed safe and tolerated. These interim results support further study using TX103 to enhance the survival outcomes.