CAR T Cells for Breast Cancer

Overseen By Valentina Hoyos, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Systemic corticosteroids

Disqualifiers: Pregnancy, Infections, Brain metastases, others

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

Compensation: Varies

Number of Visits: 6

Duration: 1 day

27 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any conventional or investigational therapy for 3 weeks before starting the study. If you are using systemic corticosteroids, you may need to stop if the dose is higher than a certain level.

What data supports the effectiveness of the treatment HTR2 T Cells for breast cancer?

Research shows that similar treatments, like CAR T-cells targeting HER2, have been effective in killing breast cancer cells in lab studies and reducing tumor size in mice. This suggests that CAR T-cell therapies could be promising for treating breast cancer. ^{1 2 3 4 5}

Is CAR T-cell therapy safe for humans?

CAR T-cell therapy, including HER2 CAR T-cells for breast cancer, has shown potential but can cause serious side effects like cytokine release syndrome (a severe immune reaction) and neurological issues. While these treatments have been effective for some cancers, they come with risks that need careful management. ^{6 7 8 9 10}

How does the CAR T cell treatment differ from other breast cancer treatments?

CAR T cell treatment for breast cancer is unique because it involves genetically modifying a patient's own T cells to specifically target and kill cancer cells that overexpress the HER2 protein, which is often associated with aggressive tumors. This approach is different from traditional treatments like surgery or chemotherapy, as it uses the body's immune system to fight cancer. ^{1 2 3 4 9}

What is the purpose of this trial?

The purpose of this study is to find the biggest dose of HTR2 T cells that is safe, to see how long these cells last in the body, to learn the side effects, and to see if these cells are able to fight and kill HER2 expressing breast cancer. Patients eligible for this study have metastatic breast cancer that has HER2 expression and has progressed on at least one line of therapy. This is a gene transfer research study using special immune cells called T cells. T cells are a type of white blood cell that helps the body recognize and fight cancer cells. The body has different ways of fighting diseases and no single way seems perfect for fighting cancer. This research combines two different ways of fighting cancer: antibodies and T cells. Antibodies are proteins that protect the body from infectious disease and possibly cancer. T cells, or T lymphocytes, are special blood cells that can kill other cells, including tumor cells. Both antibodies and T cells have shown promise treating cancer but have not been strong enough to cure most patients. Previous research has found that investigators can put genes into T cells that helps them recognize cancer cells and kill them. Investigators now want to see if by putting a new gene in those T cells to help recognize breast cancer cells expressing HER2 can kill the cancer cells. In clinical trials for various cancer types that express HER2, our center engineered a CAR that recognizes HER2 and put this CAR into patients own T cells and gave them back. Investigators saw that the cells did grow and patients did tolerate and respond to the treatment. Investigators will add a gene to the HER2 recognizing CAR T cells that will improve the T cells function. Investigators know that some immune cells in the body can lower T cells ability to kill cancer cells. Investigators have identified an antibody that will inactivate those immune suppressive cells thereby allowing T cells to survive better to recognize and kill cancer cells. This antibody targets the Trail-R2 receptor and is referred to as TR2. Also, investigators know that T cells need the support of cytokines to perform their immune functions. There is evidence showing that the addition of interleukin 15 (IL15) enhances CAR T cells ability to kill cancer cells. As a result, investigators also added IL15 to the HER2 and TR2 targeting CAR T cells (HTR2 T cells). The HTR2 T cells are an investigational product not approved by the Food and Drug Administration.

Research Team

Valentina Hoyos, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for individuals with metastatic breast cancer that expresses HER2 and has worsened despite treatment. Participants must have already tried at least one therapy line. The study involves genetically modified T cells, which are part of the immune system, to target and kill cancer cells.

Inclusion Criteria

Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Bilirubin ≤ 3x upper limit of normal

AST and ALT ≤ 3x upper limit of normal

Exclusion Criteria

Procurement: Known pregnancy or actively breast feeding

I do not have any ongoing serious infections.

I am currently taking a high dose of steroids daily.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a single infusion of HTR2 T cells, with potential for repeat infusion based on response and tolerance

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored weekly for dose-limiting side effects of the HTR2 T cells

4 weeks

4 visits (in-person)

Extended Follow-up

Participants are monitored every 3 months for the first year and every 6 months for years 1 to 5, then annually for up to 15 years

15 years

Multiple visits (in-person)

Treatment Details

Interventions

• HTR2 T Cells

Trial Overview The trial tests HTR2 T cells, a new type of treatment where patients' own T cells are engineered to better recognize and attack HER2 expressing breast cancer. It includes adding genes for a special receptor (TRAIL-R2) and interleukin 15 (IL15) to enhance the T cells' effectiveness.

Participant Groups

Group I: Arm B: HTR2 T Cells (with lymphodepletion) Experimental Treatment 1 Intervention

Two dose levels will be evaluated in Arm B (with lymphodepletion)

Group II: Arm A: HTR2 T Cells (without lymphodepletion) Experimental Treatment 1 Intervention

Two dose levels will be evaluated in Arm A (without lymphodepletion)

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Findings from Research

The third generation H1-2 CAR-T cells were successfully developed and demonstrated a high cytotoxicity rate of 90.1% against HER2(+) breast cancer cells, significantly outperforming their effect on HER2(-) cells, which had a cytolytic rate of only 13.5%.

In vivo studies using NOD/SCID mice showed that H1-2 CAR-T cells effectively inhibited tumor growth, with treated tumors weighing significantly less than those in control groups, indicating their potential as a targeted therapy for HER2(+) cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Specific cytotoxicity of a novel HER2-based chimeric antigen receptor modified T lymphocytes against HER2-positive tumor cells]. Tang, HJ., Liu, YQ., Bian, XC., et al.[2019]

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]

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]

The study successfully developed CAR-T cells that target the ERBB2 antigen, which is overexpressed in aggressive breast cancer cells, demonstrating increased apoptosis in the SKBR3 breast cancer cell line when co-cultured with these engineered T-cells.

This approach shows promise as a universal immunotherapy by enhancing T-cell activation and cytotoxicity without relying on traditional immune recognition mechanisms, suggesting potential for effective treatment of ERBB2-positive breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells. Munisvaradass, R., Kumar, S., Govindasamy, C., et al.[2018]

HER2 CAR T-cell therapy shows promise for treating solid tumors, particularly in cancers like breast cancer, but it carries significant risks of severe side effects, such as cytokine release syndrome due to targeting HER2 on non-cancerous tissues.

The review highlights ongoing efforts to enhance the safety of HER2 CAR therapies through novel designs and alternative CAR host selections, aiming to minimize the risk of toxicities while maintaining therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Driving better and safer HER2-specific CARs for cancer therapy. Liu, X., Zhang, N., Shi, H.[2019]

Chimeric-antigen-receptor T cells (CAR-T) targeting CD19 are associated with several adverse drug reactions (ADRs), with the most common being cytokine release syndrome (CRS), neurological disorders, and hematological disorders, as identified in a study analyzing 1783 safety reports.

While CAR-T therapy can lead to severe ADRs, particularly in the week following administration, the overall fatality rate from these reactions is relatively low at 5.5%, though serious conditions like hemophagocytic-lymphohistiocytosis and infections require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study. Dolladille, C., Ederhy, S., Ezine, E., et al.[2021]

CD19+ CAR T-cells have shown high effectiveness against various cancers, but their complete risk profile, including complications, was not fully understood during initial clinical trials.

Emerging evidence from post-approval studies reveals significant complications associated with CD19+ CAR T-cell therapy, such as cytokine release syndrome and neurotoxicity, indicating that these therapies can affect multiple organ systems and may lead to long-term health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after CD19+ CAR T-Cell Therapy. Penack, O., Koenecke, C.[2020]

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]

CAR-T cell therapy has significantly improved treatment outcomes for patients with relapsed and refractory hematologic cancers, but it can also lead to serious toxicities, which are primarily caused by T-cell activation and interactions with non-cancerous cells.

The review emphasizes the need for early recognition and management of CAR-T related toxicities, as well as the potential for expanding CAR-T therapies to target solid tumors in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications. Mucha, SR., Rajendram, P.[2023]

References

1. China pubmed.ncbi.nlm.nih.gov

[Specific cytotoxicity of a novel HER2-based chimeric antigen receptor modified T lymphocytes against HER2-positive tumor cells]. [2019]

2. China pubmed.ncbi.nlm.nih.gov

New approaches in chimeric antigen receptor T-cell therapy for breast cancer. [2020]

3. Netherlands 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. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Targeting and suppression of HER3-positive breast cancer by T lymphocytes expressing a heregulin chimeric antigen receptor. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Driving better and safer HER2-specific CARs for cancer therapy. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Complications after CD19+ CAR T-Cell Therapy. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

New Approaches in CAR-T Cell Immunotherapy for Breast Cancer. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications. [2023]