TAA-specific CTLs for Breast Cancer

(TACTIC Trial)

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Baylor College of Medicine

Must not be taking: Systemic corticosteroids

Disqualifiers: Severe infection, HIV, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 6-12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for breast cancer that has returned after standard treatments. It uses special immune cells called TAA-specific cytotoxic T lymphocytes, a type of immunotherapy, which target and attack cancer cells more precisely. The researchers aim to assess the treatment's effectiveness, identify any side effects, and understand its potential benefits. Suitable candidates for this trial include those with breast cancer that has spread or cannot be surgically removed and who have already tried at least two other treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to the development of potentially effective therapies.

Will I have to stop taking my current medications?

The trial requires that you stop any investigational therapy for one month and any conventional therapy for at least one week before starting the study treatment. If you are on systemic corticosteroids, you must stop them at least 48 hours before participating.

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

Research has shown that special immune cells called TAA-specific cytotoxic T lymphocytes (TAA-CTLs) have been well-tolerated in past studies. These cells target proteins known as tumor-associated antigens, primarily found on cancer cells. In other studies involving various cancer types, participants who received TAA-CTLs reported only minor side effects. Although this treatment remains experimental and lacks FDA approval, clinical trials suggest it is generally safe. So far, the treatment has not caused many serious problems in patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TAA-specific CTLs for breast cancer because they offer a targeted approach that differs from traditional treatments like chemotherapy, radiation, or hormone therapy. TAA-specific CTLs are immune cells engineered to recognize and attack tumor-associated antigens found on cancer cells, potentially improving precision in targeting the cancer without harming healthy cells. This targeted mechanism could lead to fewer side effects and improved outcomes, making it a promising option for patients who have limited success with conventional therapies.

What evidence suggests that TAA-specific CTLs might be an effective treatment for breast cancer?

Research has shown that a type of immune cell, called TAA-specific cytotoxic T lymphocytes (CTLs), may help treat certain cancers, including breast cancer. These special cells target proteins known as tumor-associated antigens (TAAs), which are mostly found on cancer cells. Early studies suggest that using these cells in treatment can be safe and might work well. In this trial, participants will receive TAA-specific CTLs as therapy for breast cancer. For example, in other cancers, patients treated with TAA-CTLs showed good results, with 73% not experiencing cancer progression for six months. This suggests that TAA-CTLs might help control cancer growth by specifically attacking cancer cells while leaving normal cells unharmed. ^{1 2 4 5 6}

Who Is on the Research Team?

Mothaffar Rimawi, MD

Principal Investigator

Baylor College of Medicine

Anne Leen, PhD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with breast cancer that has returned and is now metastatic or locally advanced and untreatable by surgery. They must have tried at least two treatments, have a life expectancy of 12+ weeks, stable organ function, no severe infections or uncontrolled conditions, not be on steroids or HIV positive, and agree to use effective birth control.

Inclusion Criteria

My breast cancer is spreading and treatments haven’t worked.

My breast cancer cannot be removed by surgery and has spread.

My kidney function, measured by creatinine, is normal for my age.

Exclusion Criteria

I have not taken steroids for at least 48 hours.

You have a serious ongoing infection.

You have a current HIV infection.

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 TAA-specific cytotoxic T lymphocytes with initial two doses four weeks apart, followed by up to six additional doses if tumor reduction is observed

6-12 months

Multiple visits for infusions and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood tests and imaging studies

1 year

Regular visits for blood tests and imaging

Long-term follow-up

Annual contact for up to 4 additional years to evaluate disease response

4 years

What Are the Treatments Tested in This Trial?

Interventions

• TAA-specific CTLs

Trial Overview The study tests TAA-specific cytotoxic T lymphocytes (TAA-CTLs), an experimental therapy targeting five common tumor-associated antigens (TAAs) in breast cancer cells. The goal is to evaluate the effectiveness and side effects of this new treatment in patients whose cancer has resisted standard therapies.

How Is the Trial Designed?

Group I: TAA-Specific CTLs Experimental Treatment 1 Intervention

Patients receiving TAA-specific CTLs as therapy for breast cancer.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Cancer Prevention Research Institute of Texas

Collaborator

Trials

55

Recruited

98,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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

In a first-in-human trial involving 15 patients with relapsed or refractory solid tumors, tumor-associated antigen cytotoxic T cells (TAA-Ts) were administered safely without any dose-limiting toxicities, demonstrating a promising new therapeutic approach.

Of the evaluable patients, 73% showed stable disease or better at day 45 post-infusion, with 6 patients remaining progression-free for a median of 13.9 months, indicating that TAA-Ts can effectively stabilize disease and prolong time to progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study. Hont, AB., Cruz, CR., Ulrey, R., et al.[2020]

Cytotoxic T lymphocytes (CTLs) play a crucial role in fighting cancer by recognizing tumor-specific antigens, which are presented by cells in the body.

The review discusses the development of peptide-based vaccines that target these tumor-associated antigens, highlighting their potential to enhance the immune response against cancer and improve CTL therapy in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tumor antigen-specific cytotoxic T lymphocytes and cancer immunotherapy - review]. Liu, Y.[2016]

In a first-in-human trial involving 10 heavily pre-treated patients with relapsed or metastatic breast cancer, multi-antigen-targeted T cells (multiTAA-T) were well tolerated with no treatment-related toxicities, indicating a promising safety profile for this therapy.

One patient experienced prolonged disease stabilization for 5 months, which was linked to the in vivo expansion and persistence of T cells targeting specific tumor antigens, along with evidence of broader immune activation against non-targeted tumor antigens in 7 out of 10 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer. Hoyos, V., Vasileiou, S., Kuvalekar, M., et al.[2022]

Tumor-associated antigen-specific cytotoxic T lymphocytes (TAA-CTL) were safely generated and infused into patients with multiple myeloma and non-Hodgkin lymphoma, with no significant adverse reactions reported during the treatment.

In a small group of 7 patients, TAA-CTL therapy showed promising efficacy, as 5 patients experienced positive clinical effects, and an increase in specific immune responses was observed 2-3 weeks post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma]. Li, XH., Xue, L., Xu, H., et al.[2020]

In a study involving 9 patients with acute myeloid leukemia (AML) at high risk of relapse, the infusion of tumor-associated antigen-specific cytotoxic T lymphocytes (TAA-CTLs) showed promising safety, with no significant adverse reactions reported during or after treatment.

The TAA-CTL therapy demonstrated an antileukemic effect in 2 out of 5 patients who were minimal residual disease (MRD) positive, indicating potential efficacy in reducing leukemia without the need for additional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells targeting multiple tumor-associated antigens as a postremission treatment to prevent or delay relapse in acute myeloid leukemia. Xue, L., Hu, Y., Wang, J., et al.[2022]

Citations

1. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/50/NCT03093350/Prot_SAP_000.pdf

TUMOR-ASSOCIATED ANTIGEN (TAA)-SPECIFIC ... TUMOR-ASSOCIATED ANTIGEN (TAA)-SPECIFIC CYTOTOXIC T LYMPHOCYTES. ADMINISTERED ... This study will evaluate the clinical efficacy of T cells specific for all 5 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9336570/

Current State of Cell Therapies for Breast Cancer - PMC NCT03093350 is one of the only BC–specific clinical trials looking at TAA-specific cytotoxic T lymphocyte treatment efficacy and safety in 12 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1044579X20301152

T-cell-based breast cancer immunotherapy In this review, we highlight the current state of using T cells as both markers for clinical practice and therapeutic options for BC.

4. withpower.com withpower.com/trial/phase-1-neoplasms-10-2021-e9dbf

TAA-T Cell Therapy for Solid Cancers TAA-T cell therapy has been studied in early trials for various cancers, including solid tumors and breast cancer, and is considered potentially nontoxic.

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.19.00177?keyword=overactive%252525252525252525252525252525252525252bbladder%252525257E%252525252525252525252525252525252525252bbotox%252525252525252525252525252525252525252band%252525252525252525252525252525252525252bneuromodulation

Immunotherapy of Relapsed and Refractory Solid Tumors ... Patients who were treated at the highest dose level showed the best clinical outcomes, with a 6-month progression-free survival of 73% after TAA-T infusion ...

6. nature.com nature.com/articles/s41392-023-01674-3

Therapeutic cancer vaccines: advancements, challenges ... Therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens, including tumor-associated antigens and tumor- ...