69 Participants Needed

CAR T-Cell Therapy for Breast Cancer

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JM
Overseen ByJoanne Mortimer, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Minerva Biotechnologies Corporation
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This trial uses a patient's own immune cells, which are modified in a lab to better recognize and attack cancer cells. The treatment targets patients with advanced breast cancer that expresses a specific protein called MUC1*. The modified T cells are designed to find and destroy these cancer cells by recognizing the MUC1* marker. MUC1 is a cancer-associated antigen that is overexpressed and modified by tumor cells in over half of all cancer cases, and it has been pursued as a target for immunotherapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients who require ongoing daily corticosteroid therapy at a dose of more than 15 mg of prednisone per day. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment huMNC2-CAR44 CAR T cells for breast cancer?

Research shows that CAR T-cell therapy, similar to huMNC2-CAR44, has been effective in targeting and killing breast cancer cells, particularly those overexpressing certain proteins like HER2. Studies have demonstrated that CAR T-cells can promote anti-breast cancer activity in both laboratory and animal models, suggesting potential effectiveness for breast cancer treatment.12345

What safety data exists for CAR T-Cell Therapy in humans?

CAR T-Cell Therapy has been associated with several safety concerns, including cytokine release syndrome (a severe immune reaction), neurotoxicity, and other organ-related toxicities. These adverse effects can vary in severity and are influenced by factors like the type of CAR T-cell used and the patient's condition.678910

What makes the huMNC2-CAR44 CAR T-cell treatment unique for breast cancer?

The huMNC2-CAR44 CAR T-cell treatment is unique because it involves genetically modified T-cells that are designed to specifically target and attack breast cancer cells, potentially offering a new approach for patients who do not respond to traditional therapies like surgery, chemotherapy, or radiation.234511

Research Team

Joanne Mortimer, M.D., F.A.C.P., F.A.S ...

Joanne E Mortimer, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with advanced breast cancer that tests positive for a specific protein, MUC1*. Participants must have tried standard treatments and be in good enough health to give consent. Women of childbearing age need a negative pregnancy test and all fertile participants must agree to use contraception. People can't join if they're on high-dose steroids, have certain blood counts or organ dysfunction, untreated brain metastases, active infections, other cancers needing treatment, severe heart issues or are HIV positive.

Inclusion Criteria

I can understand and sign a consent form.
I have had at least 3 treatments for HER2 positive breast cancer.
My breast cancer diagnosis and hormone receptor status are confirmed by a pathology review.
See 9 more

Exclusion Criteria

Treatment with investigational agent(s) within 30 days of planned lymphodepletion.
I have another cancer that is getting worse or needs treatment.
Breast-feeding women.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either huMNC2-CAR44 or huMNC2-CAR22 T cells, which are autologous T cells engineered to target MUC1*

35 days
1 visit (in-person) for T cell infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, including in vivo persistence of CAR T cells

365 days

Long-term follow-up

Participants are monitored for antitumor activity and long-term safety

Up to 15 years

Treatment Details

Interventions

  • huMNC2-CAR44 CAR T cells
Trial OverviewThe study is testing two types of CAR T cell therapies (huMNC2-CAR44 or huMNC2-CAR22) designed to target the MUC1* protein on breast cancer cells. It's an early-phase trial to see how safe these therapies are and how well they work against this form of breast cancer.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: Triple NegativeExperimental Treatment1 Intervention
Dose Expansion - 15 patients will be enrolled with triple negative metastatic breast cancer.
Group II: LuminalExperimental Treatment1 Intervention
Dose Expansion - 15 patients will be enrolled with luminal (hormone receptor positive, HER2 negative) metastatic breast cancer.
Group III: HER2+Experimental Treatment1 Intervention
Dose Expansion - 15 patients will be enrolled with HER2+ metastatic breast cancer.
Group IV: Dose EscalationExperimental Treatment1 Intervention
Dose escalation or de-escalation is tested in cohorts of 3 patients each using standard "3+3" dose-finding.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Minerva Biotechnologies Corporation

Lead Sponsor

Trials
1
Recruited
70+

City of Hope Medical Center

Collaborator

Trials
614
Recruited
1,924,000+

Findings from Research

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.
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]
CAR T cells engineered to express the TR2.41BB receptor can effectively overcome the immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) in breast cancer, leading to enhanced tumor cell killing and reduced tumor growth in mouse models.
The TR2.41BB CAR T cells not only restored the cytotoxic activity of CAR T cells against MUC1+ breast cancer cells but also improved T cell proliferation and persistence at the tumor site, suggesting a promising strategy for targeting solid tumors with challenging microenvironments.
Selectively targeting myeloid-derived suppressor cells through TRAIL receptor 2 to enhance the efficacy of CAR T cell therapy for treatment of breast cancer.Nalawade, SA., Shafer, P., Bajgain, P., et al.[2022]
A new CAR-NK cell therapy targeting CD44v6 has been developed, showing effective cytotoxicity against triple-negative breast cancer (TNBC) in 3D spheroid models, indicating its potential as a treatment option.
The incorporation of an IL-15 superagonist enhances the CAR-NK cells' ability to attack TNBC, while also demonstrating resistance to the immunosuppressive tumor microenvironment, suggesting a promising approach to overcoming challenges in TNBC treatment.
Next Generation CD44v6-Specific CAR-NK Cells Effective against Triple Negative Breast Cancer.Raftery, MJ., Franzén, AS., Radecke, C., et al.[2023]

References

Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells. [2018]
Selectively targeting myeloid-derived suppressor cells through TRAIL receptor 2 to enhance the efficacy of CAR T cell therapy for treatment of breast cancer. [2022]
Next Generation CD44v6-Specific CAR-NK Cells Effective against Triple Negative Breast Cancer. [2023]
New approaches in chimeric antigen receptor T-cell therapy for breast cancer. [2020]
[Specific cytotoxicity of a novel HER2-based chimeric antigen receptor modified T lymphocytes against HER2-positive tumor cells]. [2019]
Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications. [2023]
A Cross-Reactive Small Protein Binding Domain Provides a Model to Study Off-Tumor CAR-T Cell Toxicity. [2020]
Complications after CD19+ CAR T-Cell Therapy. [2020]
[Complications other than infections, CRS and ICANS following CAR T-cells therapy: Recommendations of the Francophone Society of bone marrow transplantation and cell therapy (SFGM-TC)]. [2022]
From bench to bedside: the history and progress of CAR T cell therapy. [2023]
An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment. [2022]