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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using HTR2 T cells, a type of CAR T cell therapy, to combat HER2-positive breast cancer that has spread and hasn't responded to at least one other treatment. Researchers aim to determine the safest dose, assess how long these cells remain in the body, and understand their side effects. They also seek to evaluate how effectively these cells attack and destroy cancer cells. Individuals with HER2-positive metastatic breast cancer, whose disease has worsened after standard treatment, may be suitable for this study. 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 new therapy.

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.

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

Research has shown that patients generally handled CAR T cell therapies, such as HTR2 T cells, well in past trials. These treatments enhance the body's own T cells to better combat cancer. In earlier studies, patients with HER2-positive cancers who received similar CAR T cell treatments found that the cells grew and were accepted by the body, meaning the treatment didn't cause severe side effects for most people.

However, since researchers are still testing HTR2 T cells, not all possible side effects are known. Early trials aim to find safe doses and understand how the cells behave in the body. Although the available data has not reported specific severe reactions, participants should discuss potential risks with their healthcare providers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer, which often involve chemotherapy, surgery, and hormone therapy, HTR2 T Cells offer a novel approach by harnessing the body's own immune system to fight cancer. Researchers are excited about these treatments because they involve CAR T cell therapy, where T cells are modified to better recognize and attack cancer cells. This method could provide a more targeted attack on cancer cells with potentially fewer side effects. Additionally, the trial explores two approaches: one with lymphodepletion and one without, which may offer flexibility in treatment options and effectiveness.

What evidence suggests that HTR2 T cells might be an effective treatment for breast cancer?

Research has shown that CAR T cell therapy could effectively treat cancers like HER2-positive breast cancer. Studies have found that specially engineered CAR T cells can identify and destroy cancer cells, with some patients responding well to the treatment. In this trial, participants will receive HTR2 T cells, designed to target HER2, a protein found in some breast cancer cells, and use interleukin 15 (IL15) to enhance their ability to kill these cells. Additionally, an added antibody protects the T cells from being weakened by other immune cells. This trial includes two separate arms: Arm A, where participants receive HTR2 T cells without lymphodepletion, and Arm B, where participants receive HTR2 T cells with lymphodepletion. Although researchers are still studying this treatment, early results suggest it may help the body fight HER2-positive breast cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Valentina Hoyos, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12064824/

Prognostic impact of tumor-infiltrating lymphocytes in ... Fifty percent of the patients achieved a partial response as the best response to first-line treatment. For the whole cohort, at a median follow ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12006274/

Treatment patterns and outcomes in HER2-low metastatic ... Median real-world overall survival (all patients) was 15.8 months (95% confidence interval: 15.2–16.5, median follow-up = 54.5 months) from the ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2830196

Tumor-Infiltrating Lymphocytes and Survival Outcomes in ... Similarly, patients with TILs 20% or higher had a 10-year OS rate of 89.3% in the long arm vs 93.1% in the short arm (HR, 0.36; 95% CI, 0.10- ...

4. oncologynewscentral.com oncologynewscentral.com/slideshow/wave-of-pivotal-data-hits-her2-positive-breast-cancer-care

Wave of Pivotal Data Hits HER2-Positive Breast Cancer Care At a median follow-up of 8.4 years, patients who received T-DM1 had a seven-year OS of 89.1% versus 84.4% for those who received trastuzumab ( ...

5. esmoopen.com esmoopen.com/article/S2059-7029(24)01891-X/fulltext

Tumor-infiltrating lymphocytes in HER2-positive breast ... Patients with HER2-positive breast cancers historically had worse outcomes relative to those with other breast cancer subtypes. 1. Slamon ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11763754/

The Real-World Clinical Outcomes of Heavily Pretreated ... We observed no significant difference in the ORR in patients with HER2+ compared to HER2-low metastatic breast cancer (Figure 1A). A total of 21 ...

7. mdpi.com mdpi.com/2072-6694/17/19/3172

Regulatory T Cells in Invasive Breast Cancer: Prognosis, ... In vivo studies have demonstrated that inhibiting COX-2 results in a reduction in Treg frequency and activity, as well as diminished FOXP3 expression in tumor- ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06251544

Study Details | NCT06251544 | TRAIL-R2 and HER2 Bi ... 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, ...