CAR T-Cell Therapy for Breast Cancer

Overseen By Joanne Mortimer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Minerva Biotechnologies Corporation

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune, Organ dysfunction, HIV, others

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

Compensation: Varies

Number of Visits: 1

Duration: 35 days

69 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new immunotherapy treatment called CAR T-cell therapy for advanced breast cancer. The goal is to determine if these specially engineered cells can effectively target and fight cancer cells in patients with certain types of metastatic breast cancer, including triple-negative, hormone receptor-positive, and HER2-positive types. The trial seeks individuals who have already undergone standard treatments for metastatic breast cancer and whose tumors exhibit a specific protein marker called MUC1*.

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 innovative therapy.

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.

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

Research has shown that huMNC2-CAR44 CAR T cells are being tested for safety in treating certain types of breast cancer. Although specific safety data from human studies is not yet available, this treatment is in the early stages of clinical trials. This phase focuses on safety, with researchers closely monitoring for any side effects or adverse reactions.

CAR T-cell therapies generally modify a patient's immune cells to enhance their ability to fight cancer. This method has been tried in other cancers and has shown promise with manageable side effects. However, as this is a new treatment for breast cancer, understanding its safety is a primary goal of the studies.

Participants in these trials receive close monitoring for any side effects, ensuring their safety as the treatment develops further. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

CAR T-cell therapy for breast cancer is unique because it uses the body's own immune system to target and destroy cancer cells. Unlike standard treatments like chemotherapy and hormone therapy, which attack cancer cells indirectly, CAR T-cells are engineered to directly recognize and bind to specific proteins on cancer cells, leading to their destruction. Researchers are excited about this approach because it offers a highly personalized treatment option that could potentially result in fewer side effects and more effective targeting of cancer cells, especially in difficult-to-treat cases like triple-negative and HER2-positive breast cancer. This precision-targeting mechanism could revolutionize how advanced breast cancer is treated.

What evidence suggests that huMNC2-CAR44 CAR T cells might be an effective treatment for breast cancer?

Research has shown that huMNC2-CAR44 CAR T cells are designed to specifically target and attack breast cancer cells by recognizing a protein called MUC1*. This protein appears on the surface of some breast cancer cells. In lab studies, these CAR T cells have demonstrated the ability to gather around and possibly destroy cancer cells with the MUC1* protein. Although human studies provide limited information, early results suggest this treatment might help combat cancer cells in various types of breast cancer. This trial will enroll participants in different arms to study the effects on triple negative, luminal, and HER2+ metastatic breast cancer. More research is needed to confirm these effects in patients. ^{1 4 6 7 8}

Who Is on the Research Team?

Joanne E Mortimer, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• huMNC2-CAR44 CAR T cells

Trial Overview The 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.

How Is the Trial Designed?

Group I: Triple Negative Experimental Treatment 1 Intervention

Dose Expansion - 15 patients will be enrolled with triple negative metastatic breast cancer.

Group II: Luminal Experimental Treatment 1 Intervention

Dose Expansion - 15 patients will be enrolled with luminal (hormone receptor positive, HER2 negative) metastatic breast cancer.

Group III: HER2+ Experimental Treatment 1 Intervention

Dose Expansion - 15 patients will be enrolled with HER2+ metastatic breast cancer.

Group IV: Dose Escalation Experimental Treatment 1 Intervention

Dose escalation or de-escalation is tested in cohorts of 3 patients each using standard "3+3" dose-finding.

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+

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next Generation CD44v6-Specific CAR-NK Cells Effective against Triple Negative Breast Cancer. Raftery, MJ., Franzén, AS., Radecke, C., et al.[2023]

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 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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 cells targeting the MUC1 antigen, which is overexpressed in breast cancer, demonstrated high effectiveness in recognizing and attacking MUC1+ cancer cells, showing strong antitumor activity in laboratory tests.

The study found that CAR T cells with the 41BB signaling domain outperformed those with the CD28 domain by enhancing T cell proliferation and reducing suppressive signals, suggesting that 41BB-based CAR T cells could be more effective for treating breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment. Khuisangeam, N., Jewmoung, S., Thaiwong, R., et al.[2022]

CAR-T cells targeting HER2 can cause significant off-tumor toxicities in a mouse model, with the severity of these toxicities being influenced by the type of co-stimulatory domain used, particularly CD28, which was found to be the most toxic.

The study identified that CD4+ CAR-T cells are the main contributors to these toxicities, and variations in donor T cell sources can further affect the toxicity profile, suggesting that both intrinsic CAR-T cell characteristics and donor-specific factors play a role in the safety of CAR-T therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cross-Reactive Small Protein Binding Domain Provides a Model to Study Off-Tumor CAR-T Cell Toxicity. Hammill, JA., Kwiecien, JM., Dvorkin-Gheva, A., et al.[2020]

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]

CAR T cell therapy, particularly with the approval of tisagenlecleucel, has shown remarkable efficacy in treating pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia, with six therapies approved as of April 2023 for B-cell malignancies and multiple myeloma.

However, the therapy is associated with significant adverse events like cytokine release syndrome, which are more severe with higher pretreatment tumor burdens; thus, initiating therapy early or using a debulking strategy may help mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From bench to bedside: the history and progress of CAR T cell therapy. Mitra, A., Barua, A., Huang, L., et al.[2023]

CAR-T cell therapy has been extended to treat mantle lymphoma and multiple myeloma, but it is associated with significant complications such as cardiac issues, delayed cytopenias, Graft versus Host Disease, and tumoral lysis syndrome.

A working group from the Francophone society of bone marrow transplantation and cellular therapy has developed recommendations for managing these complications, focusing on their epidemiology, mechanisms, and risk factors to improve patient care with commercial CAR-T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[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)]. Pochon, C., Courbon, C., Bay, JO., et al.[2022]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04020575

NCT04020575 | Autologous huMNC2-CAR44 or ... The investigators propose to evaluate the safety and preliminary anti-tumor activity of adoptively transferred autologous T cells genetically modified to ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS2683

First-in-human autologous CAR-T for metastatic breast ... A phase 1, first-in-human study of autologous monocytes engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants with HER2- ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10093019/

Emerging Targeted Therapies for HER2-Positive Breast Cancer HER2-positive breast cancer (BC), which accounts for ~20% of BC, is one of the more aggressive and has the worst overall survival rate among them.

4. withpower.com withpower.com/trial/phase-1-breast-neoplasms-2020-3141c

CAR T-Cell Therapy for Breast Cancer 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- ...

5. acgtfoundation.org acgtfoundation.org/news/cell-and-gene-therapy-for-breast-cancer/

Cell and Gene Therapy Research for Breast Cancer The clinical trial is testing a CAR T-cell therapy, called huMNC2-CAR44, for patients with metastatic breast cancer. The CAR T-cell therapy ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04020575/

Clinical Trial: NCT04020575 - Breast Cancer Phase I study of adoptive immunotherapy for advanced MUC1* positive breast cancer with autologous T cells engineered to express a chimeric antigen receptor.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.TPS2663

Phase I study of adoptive immunotherapy for advanced ... A phase I study evaluating the safety of adoptively transferred autologous T cells genetically modified to express huMNC2-CAR44 in patients with metastatic MUC ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7650095/

Clinical Data on Immunotherapy in Breast Cancer - PMC This review summarizes key clinical trials, recent findings, and emerging therapeutic concepts in the field of immunotherapy for breast cancer.