CAR-T Cell Therapy for Relapsing Breast Cancer

Overseen By Caroline Babinec

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: CNS involvement, Multiple metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 8 weeks

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called iC9-CAR.B7-H3 T Cell Therapy, a type of immunotherapy, for individuals with triple-negative breast cancer (TNBC) that has returned or resisted other treatments. The trial aims to determine the safety of this treatment as doses increase. The process uses patients' own immune cells, modifies them to better fight cancer, and then reintroduces them into the body. Individuals diagnosed with TNBC that does not respond to other treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that iC9-CAR.B7-H3 T cell therapy has been tested for safety in treating triple-negative breast cancer (TNBC). This treatment modifies a patient's T cells (a type of immune cell) to enhance their ability to attack cancer cells. In early studies, patients received this therapy, and researchers closely monitored its safety.

The results indicated that the therapy was generally well-tolerated. Some patients experienced side effects, which are common with such treatments. These side effects included fever and low blood counts, but they were manageable. It is important to note that these findings come from early studies focused on understanding the treatment's safety for humans. As this is a phase 1 trial, the main goal is to ensure the treatment does not cause severe harm. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for relapsing breast cancer, which often include chemotherapy, hormone therapy, and targeted therapies like HER2 inhibitors, iC9-CAR.B7-H3 T cell therapy offers a novel approach by using the body's own immune system. This experimental treatment involves genetically modifying a patient's T cells to better recognize and attack cancer cells, specifically targeting the B7-H3 protein found on many breast cancer cells. Researchers are excited about this therapy because it harnesses the power of CAR-T cell technology, which has shown promise in treating other cancers, potentially offering a more personalized and effective option for patients with difficult-to-treat forms of breast cancer.

What evidence suggests that iC9-CAR.B7-H3 T Cell Therapy might be an effective treatment for relapsing breast cancer?

Research has shown that iC9-CAR.B7-H3 T Cell Therapy, the treatment under study in this trial, is an experimental approach designed to attack the B7-H3 protein found on some cancer cells. This therapy uses specially altered T cells, a type of immune cell, to locate and destroy these cancer cells. Early studies suggest that targeting B7-H3 might aid in fighting triple-negative breast cancer (TNBC), a cancer type often difficult to treat with standard methods. Although definitive proof of its effectiveness is not yet available, this approach offers hope for treating TNBC that has recurred or is resistant to other treatments. ^{1 2 3 5 6}

Who Is on the Research Team?

Yara E Abdou, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with triple-negative breast cancer (TNBC) that has returned or hasn't responded to treatment. Participants must meet certain health standards, but specific inclusion and exclusion criteria are not provided.

Inclusion Criteria

My breast cancer is triple-negative, not showing positive for ER, PR, or HER2.

I am able to care for myself but may not be able to do active work.

Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information explained to, understood by and signed by the subject or legally authorized representative

Exclusion Criteria

Subject does not have a measurable and or evaluable disease as defined by RECIST 1.1

I have had brain issues due to cancer spread and needed radiation.

I have another cancer, but it won't affect this trial's treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Collection and Manufacturing

Cells are collected from eligible subjects to manufacture iC9-CAR.B7-H3 T cells

2-4 weeks

Lymphodepletion Chemotherapy

Participants receive lymphodepletion with cyclophosphamide and fludarabine before T cell infusion

1 week

Treatment

Participants receive escalating doses of iC9-CAR.B7-H3 T cells by infusion

Up to 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• iC9-CAR.B7-H3 T Cell Therapy

Trial Overview The study is testing the safety of increasing doses of a new therapy called iC9-CAR.B7-H3 T Cell Therapy in combination with two chemotherapy drugs, cyclophosphamide and fludarabine, in patients with TNBC.

How Is the Trial Designed?

Group I: iC9-CAR.B7-H3 T cells Experimental Treatment 3 Interventions

Specimen will be collected to prepare the iC9-CAR.B7-H3 T cells. Disease-fighting T cells will be isolated and modified to prepare the iC9-CAR.B7-H3 T cells. In part 2, the iC9-CAR.B7-H3 T cells are given by infusion after completion of lymphodepletion chemotherapy.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Bellicum Pharmaceuticals

Industry Sponsor

Trials

28

Recruited

1,400+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

CD19+ relapses of acute lymphoblastic leukemia (ALL) after anti-CD19 CAR-T cell therapy still show sensitivity to T-cell mediated lysis, indicating potential for continued treatment effectiveness.

Immunophenotyping revealed that while previously targeted antigens decreased, new targetable antigens emerged, suggesting that adapting treatment strategies based on immunophenotype analysis could improve outcomes for patients with high-risk relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two Ways of Targeting a CD19 Positive Relapse of Acute Lymphoblastic Leukaemia after Anti-CD19 CAR-T Cells. Grain, A., Ollier, J., Guillaume, T., et al.[2023]

Fourth-generation CAR T cells targeting the folate receptor alpha (FRα) showed a high efficacy in specifically killing breast cancer cells, achieving an 88.7% lysis rate in laboratory tests against the MDA-MB-231 cell line.

These CAR T cells demonstrated enhanced anti-tumor activity in three-dimensional spheroid cultures, indicating their potential effectiveness in treating advanced breast cancer by reducing tumor size and breaking apart tumor structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fourth-generation chimeric antigen receptor T cells targeting folate receptor alpha antigen expressed on breast cancer cells for adoptive T cell therapy. Luangwattananun, P., Junking, M., Sujjitjoon, J., et al.[2021]

Immunotherapy, particularly CAR-T therapy, is emerging as a promising treatment for breast cancer, which remains a leading cause of cancer-related deaths among women.

While CAR-T therapy has shown success in treating blood cancers, challenges exist in applying it to solid tumors like breast cancer; ongoing research aims to enhance its effectiveness and manage potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approaches in CAR-T Cell Immunotherapy for Breast Cancer. Wang, J., Zhou, P.[2018]

The study found that high levels of leukemia blast contamination in the starting material did not negatively impact the manufacturing of CAR T-cells or their ability to expand, suggesting that CAR T-cell therapy can be safely produced even from contaminated samples.

Using a specific CAR design with a short linker (CAR.CD19 SL) enhances the ability of CAR T-cells to target and kill CD19+ leukemia cells, providing a potential safety advantage in preventing leukemic relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts. Quintarelli, C., Guercio, M., Manni, S., et al.[2022]

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]

In a study of 80 patients with relapsed/refractory B-cell acute lymphocytic leukemia (B-ALL), humanized CD19 CAR-T cells demonstrated a higher overall response rate (87.8%) compared to murine CAR-T cells (74.2%), indicating better efficacy in treating this condition.

Both humanized and murine CAR-T therapies had similar safety profiles, with comparable rates of cytokine-release syndrome (CRS) and neurotoxicity, but humanized CAR-T therapy showed improved recurrence-free survival in patients with a higher tumor burden in the bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term follow-up of humanized and murine CD19 CAR-T-cell therapy for B-cell acute lymphoblastic leukemia]. Du, MY., Zhang, YQ., Liao, DY., et al.[2023]

CAR T-cell therapy has shown promising results in treating hematologic malignancies and is being explored as a potential treatment for breast cancer, which remains a leading cause of cancer death among women.

Preclinical studies indicate that CAR T-cells can enhance anti-breast cancer activity both in laboratory settings and in living organisms, suggesting they may be an effective therapeutic option for breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New approaches in chimeric antigen receptor T-cell therapy for breast cancer. Zhang, Q., Ding, B., Qian, L., et al.[2020]

In a study involving five adults with relapsed B cell acute lymphoblastic leukemia (B-ALL), treatment with autologous T cells modified to express a CD19-specific CAR (19-28z) led to rapid tumor eradication and complete remissions without minimal residual disease (MRD), indicating strong efficacy of this therapy.

The treatment was generally well tolerated, although patients with higher tumor burdens experienced significant cytokine elevations, which required management with steroids, highlighting the need for monitoring and potential intervention during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Brentjens, RJ., Davila, ML., Riviere, I., et al.[2023]

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]

In a study of 43 patients with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) who relapsed after an allotransplant, 79% achieved complete remission after receiving allogeneic anti-CD19 CAR-T cells, indicating high efficacy of this treatment.

While the therapy was effective, it was associated with a high incidence of cytokine release syndrome (CRS) in 88% of patients, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant. Zhang, C., Wang, XQ., Zhang, RL., et al.[2021]

CAR-T cell therapy has shown remarkable efficacy in treating B cell malignancies, including leukemia, lymphoma, and multiple myeloma, with high response rates, but it comes with significant safety concerns.

The most serious side effects of CAR-T therapy are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which require supportive care and specific treatments like tocilizumab and steroids to manage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy: the Efficacy and Toxicity Balance. Chohan, KL., Siegler, EL., Kenderian, SS.[2023]

CAR-T therapy has shown significant success in treating relapsed/refractory B-cell malignancies, utilizing genetically modified T-cells to target and eliminate cancer cells effectively.

Despite its efficacy, CAR-T therapy is associated with serious toxicities such as cytokine release syndrome and neurotoxicity, necessitating improved safety measures, especially as the therapy is being tested in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building safety into CAR-T therapy. Peters, DT., Savoldo, B., Grover, NS.[2023]

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]

CAR-T cell therapy has shown remarkable success in treating B-cell malignancies, but researchers are focused on improving its safety and effectiveness due to risks like cytokine release syndrome and off-target effects.

Innovative safety strategies, such as ON- and OFF-switch CARs and multi-antigen-targeting CAR-T cells, are being developed to enhance the persistence and reduce adverse events associated with CAR-T therapy, paving the way for a new generation of treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering Next-Generation CAR-T Cells for Better Toxicity Management. Andrea, AE., Chiron, A., Bessoles, S., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06347068

Study of Autologous CAR-T Cells Targeting B7-H3 in ... T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (iC9-CAR.B7-H3 T cells) treatment is experimental and has not been approved by the ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-02642

Genetically Engineered Cells (iC9-CAR.B7-H3 T cells) for ... This phase I trial tests the safety, side effects, and best dose of iC9-CAR.B7-H3 T cells in treating patients with triple negative breast cancer (TNBC) ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12107568/

B7-H3 and CSPG4 co-targeting as Pan-CAR-T cell ... Chimeric antigen receptor T (CAR-T) cell therapy is under clinical investigation in patients with metastatic triple-negative breast cancer (TNBC).

4. trialx.com trialx.com/clinical-trials/listings/310538/study-of-autologous-car-t-cells-targeting-b7-h3-in-tnbc-ic9-carb7-h3-t-cells/

Study of Autologous CAR-T Cells Targeting B7-H3 in ... This phase 1, single-center, open-label study explores the safety of escalating doses of chimeric antigen receptor T cells (CAR-T) cells in ...

5. unclineberger.org unclineberger.org/cellular-immunotherapy/clinical-trials/

Clinical Trials - Adult and Pediatric Trials The purpose of this study is to test the safety and tolerability of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against ...

6. researchgate.net researchgate.net/publication/392683962_Abstract_P1-07-22_Phase_I_Study_of_B7-H3_Specific_Chimeric_Antigen_Receptor_CAR_T_Cell_Therapy_in_Patients_with_Triple-Negative_Breast_Cancer

Abstract P1-07-22: Phase I Study of B7-H3 Specific ... Methods: This is a Phase I, single-center, open-label study designed to evaluate the safety of escalating doses of CAR T cells targeting the B7- ...