T-Cell Therapy for Breast Cancer

Not currently recruiting at 9 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment using modified T cells, which are special blood cells, to target metastatic breast cancer. The goal is to determine the right dose of these T cells for patients whose cancer lacks the HER2 protein. Participants should have breast cancer that has progressed after at least one round of chemotherapy and should express a protein called mesothelin on their cancer cells. As a Phase 1 trial, this research aims to understand 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 chemotherapy, targeted therapy, or radiotherapy at least 14 days before receiving T-cells, and any prior immunotherapy must be completed more than a month before the T-cell infusion. If you are on daily systemic corticosteroids or other immunosuppressive agents, you will need to stop those as well.

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

Research has shown that T cells targeting mesothelin have been safe in earlier studies. One study found that patients with various cancers, such as breast cancer, experienced no negative side effects after receiving these T cells. Another study tested the safety of these T cells in patients with solid tumors expressing mesothelin. These findings suggest the treatment is generally well-tolerated.

However, this trial remains in its early stages. Early trials primarily focus on safety, so while initial results appear promising, further testing is necessary to confirm them. Researchers will closely monitor participants to ensure their safety throughout the trial.12345

Why are researchers excited about this trial's treatments?

Unlike standard treatments for breast cancer, which typically involve surgery, chemotherapy, or radiation, mesothelin-targeted T-cell therapy offers a novel approach by harnessing the body's immune system to attack cancer cells. This treatment works by modifying T cells to specifically target and destroy cells that express mesothelin, a protein often found in abundance on the surface of cancer cells. Researchers are excited about this therapy because it represents a targeted, potentially more precise way to combat cancer with fewer side effects compared to traditional treatments. Additionally, the ability to tailor the timing of T-cell infusion for each patient adds a personalized element to the therapy, potentially increasing its effectiveness.

What evidence suggests that this trial's treatments could be effective for metastatic HER2-negative breast cancer?

Research has shown that a new approach using specially modified T cells, which participants in this trial will receive, holds promise for treating certain types of breast cancer. In one study, these T cells proved very effective against triple-negative breast cancer, a particularly aggressive type. Another study found that about 30% of breast cancer cases have a protein called mesothelin, which these T cells target. This finding suggests that focusing on mesothelin could be a useful strategy to combat some breast cancers. While more research is needed, the early results offer hope for those with tumors containing mesothelin.12346

Who Is on the Research Team?

Shanu Modi, MD - MSK Breast Medical ...

Shanu Modi, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced HER2-negative breast cancer who've had at least one chemo treatment and whose disease has progressed. They must have finished any previous treatments, including immunotherapy, certain days before getting T-cells and agree to use contraception. People can't join if they're on daily steroids, have autoimmune diseases, are pregnant or breastfeeding, or have untreated brain metastases.

Inclusion Criteria

I finished chemotherapy at least a week ago.
I finished chemotherapy, targeted therapy, or radiotherapy at least 14 days ago and any immunotherapy over a month ago.
Ability to understand and provide written, informed consent for the study
See 15 more

Exclusion Criteria

Pregnancy or lactation
I have not taken antibiotics for an infection in the last 7 days.
I have an autoimmune or antibody-mediated disease.
See 8 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Leukapheresis for harvesting PBMCs and administration of cyclophosphamide

1 week
1 visit (in-person)

Treatment

Infusion of mesothelin-targeted T cells and inpatient monitoring

2 days
1 visit (in-person, inpatient)

Follow-up

Participants are monitored weekly as outpatients for safety and effectiveness

8 weeks
8 visits (in-person)

Long-term follow-up

Participants are monitored for long-term safety and effectiveness

2 years

What Are the Treatments Tested in This Trial?

Interventions

  • AP1903
  • Cyclophosphamide
  • Mesothelin-targeted T cells
Trial Overview The study tests different doses of modified T cells targeting mesothelin in patients with metastatic breast cancer to find a safe level. Patients will receive Cyclophosphamide followed by the engineered T cells and AP1903 as part of the treatment process.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: T-cell infusionExperimental Treatment3 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

United States Department of Defense

Collaborator

Trials
940
Recruited
339,000+

Published Research Related to This Trial

Two types of mesothelin-directed CAR T cells were tested in mouse models of ovarian cancer, showing that while M28z CAR T cells improved survival, they did not achieve lasting tumor control, whereas MBBz CAR T cells led to long-term remission in some cases.
The study revealed that the tumor microenvironment negatively affects CAR T cell persistence due to the upregulation of inhibitory pathways, highlighting the need for strategies to enhance CAR T cell effectiveness in ovarian cancer treatment.
Mesothelin-Specific CAR T Cells Target Ovarian Cancer.Schoutrop, E., El-Serafi, I., Poiret, T., et al.[2021]
Meso3 CAR T cells, targeting the membrane-proximal region of mesothelin, showed superior activation and cytokine production compared to meso1 CAR T cells, indicating a more effective immune response against cancer cells.
In animal models, meso3 CAR T cells demonstrated stronger antitumor effects in gastric and ovarian cancers, suggesting that this approach could be a more effective immunotherapy for treating mesothelin-positive solid tumors.
Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor.Zhang, Z., Jiang, D., Yang, H., et al.[2021]
The study developed fully human anti-mesothelin CAR T cells that effectively target and kill mesothelin-expressing tumors, demonstrating strong cytolytic functions and the ability to produce proinflammatory cytokines in vitro.
In a xenogenic model of human ovarian cancer, the transfer of these human CAR T cells led to significant tumor regression, even in the presence of high levels of soluble mesothelin, suggesting they can overcome challenges related to transgene immunogenicity seen with mouse-derived CARs.
Redirected antitumor activity of primary human lymphocytes transduced with a fully human anti-mesothelin chimeric receptor.Lanitis, E., Poussin, M., Hagemann, IS., et al.[2021]

Citations

Mesothelin-targeted CAR-T cells secreting NKG2D-BiTEs ...Mesothelin-targeted CAR-T cells secreting NKG2D-BiTEs exhibit potent efficacy against triple-negative breast cancer. Muhammad Auwal Saliu ...
A phase I trial of regional mesothelin-targeted CAR T-cell ...We therefore initiated an open-label, dose-escalating, single-center, first-in-human phase I trial of intrapleural delivery of mesothelin-targeted CAR T cells ...
Mesothelin-targeting T cell receptor fusion construct ...This trial was an open-label, first-in-human, multicenter phase 1 study in patients with treatment-refractory, mesothelin-expressing cancers.
Mesothelin expression and survival outcomes in triple ...A single study has evaluated mesothelin expression in all breast cancer subtypes and showed that mesothelin was expressed in 30% of the cases, ...
Mesothelin Expression and Survival Outcomes in Triple ...The aim of this study was to evaluate mesothelin expression in triple-negative breast cancer (TNBC) and its correlation with survival outcomes.
Study Details | NCT05623488 | CAR T Cells in Mesothelin- ...This is a phase I study to establish the safety and feasibility of lentiviral transduced CAR T cell products in patients with mesothelin expressing breast ...
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