Nivolumab + Chemotherapy for Triple-negative Breast Cancer

Not currently recruiting at 1 trial location

Overseen By Andrew Davis, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: Metastatic disease, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of drugs—carboplatin, nivolumab, and paclitaxel—to determine their effectiveness in treating triple-negative breast cancer, an aggressive form of the disease. Researchers aim to discover if this combination can create a more favorable immune environment for treatment by reducing certain immune cells (tumor-associated macrophages) and boosting others (tumor-infiltrating lymphocytes). It suits those newly diagnosed with early-stage triple-negative breast cancer that remains untreated. Participants should have a tumor size of at least 2 cm and be eligible for chemotherapy before surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic immunosuppressive medications or other investigational agents, and certain conditions like uncontrolled infections or autoimmune diseases may affect eligibility.

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

A previous study tested the combination of nivolumab, carboplatin, and paclitaxel for safety and effectiveness in treating breast cancer. The research showed that this combination is generally well-tolerated. Most patients experienced mild to moderate side effects common with chemotherapy, such as tiredness, nausea, and hair loss, while more serious side effects were less common.

Research also examined adding cabiralizumab to this combination. It was tolerable for most patients, but cabiralizumab is no longer part of the current study. The common side effects were similar to those of regular chemotherapy, like tiredness and nausea.

Overall, these treatments have been studied enough to suggest they are safe for many people, but individual experiences can vary. It's always important to discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for triple-negative breast cancer?

Researchers are excited about the treatment involving nivolumab combined with chemotherapy for triple-negative breast cancer because it introduces an innovative approach to cancer treatment by harnessing the immune system. Unlike traditional chemotherapy alone, which directly targets cancer cells, nivolumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combination aims to enhance the body's natural defenses, potentially leading to improved outcomes. Additionally, the use of nivolumab offers a novel mechanism compared to standard chemotherapy regimens, which might result in better efficacy and possibly fewer side effects in some patients.

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

This trial will evaluate the combination of nivolumab with chemotherapy drugs such as carboplatin and paclitaxel for triple-negative breast cancer (TNBC). Studies have shown that using nivolumab with these chemotherapy drugs can shrink tumors in TNBC. Research indicates that this combination can lead to a "pathological complete response," where no cancer is found in tissue samples after treatment. This outcome suggests the treatment is effective. Nivolumab enhances the immune system's ability to fight cancer cells. The goal of combining these treatments is to strengthen the body's immune response to better attack the cancer. Overall, early research suggests this approach is effective for TNBC patients. ^{1 4 5 6 7}

Who Is on the Research Team?

Andrew Davis, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with early stage triple-negative breast cancer who are fit (ECOG ≤ 1), have not had previous treatments, and whose organs function normally. They must be able to consent, follow the study plan, and agree to use contraception if of childbearing potential. Exclusions include certain autoimmune diseases, other cancers unless in remission under conditions, uncontrolled illnesses or infections, recent immunosuppressants use or major surgery.

Inclusion Criteria

I am willing and able to follow the trial's schedule and tests.

I am fully active or have some restrictions but can still care for myself.

I have not received any treatment for my current illness.

Exclusion Criteria

You have a condition that causes abnormal bleeding or blood clotting.

I had cancer other than breast cancer but meet the survivor criteria.

History of allergic reactions to specified compounds

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant chemotherapy with paclitaxel and carboplatin, and nivolumab for 12 weeks

12 weeks

Weekly visits for paclitaxel, every 3 weeks for carboplatin, every 2 weeks for nivolumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Long-term follow-up

Participants are monitored for recurrence-free survival

3 years and 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Blood draw
• Bone marrow
• Carboplatin
• Nivolumab
• Paclitaxel
• Tumor biopsy

Trial Overview The trial tests if adding nivolumab to standard neoadjuvant chemotherapy before surgery can change immune cells in tumors (decrease TAMs and increase TILs) compared to just chemotherapy alone. This could potentially improve outcomes for patients with localized triple-negative breast cancer.

How Is the Trial Designed?

Group I: Unrandomized Arm: Neoadjuvant Chemo + Nivolumab Experimental Treatment 6 Interventions

* As of Amendment #7 IRB approved 10/13/2022: The study will no longer enroll to Arm B. Cabiralizumab will no longer be given. Remaining patients will be enrolled in single arm study. * Neoadjuvant chemotherapy consists of paclitaxel and carboplatin. Paclitaxel will be given intravenously (IV) at a dose of 80 mg/m\^2 on a weekly basis for 12 weeks. Carboplatin will be given IV at a dose of AUC 5 every 3 weeks for 12 weeks. Nivolumab will be given IV at a dose of 240 mg every 2 weeks for 12 weeks. Nivolumab will be administered first, followed by carboplatin, followed by paclitaxel.

Group II: Arm B: Neoadjuvant chemo + nivolumab + cabiralizumab Experimental Treatment 7 Interventions

As of Amendment #7 IRB approved 10/13/2022: The study will no longer enroll to Arm B. Cabiralizumab will no longer be given. * Neoadjuvant chemotherapy consists of paclitaxel and carboplatin. Paclitaxel will be given intravenously (IV) at a dose of 80 mg/m\^2 on a weekly basis for 12 weeks. Carboplatin will be given IV at a dose of AUC 5 every 3 weeks for 12 weeks. Nivolumab will be given IV at a dose of 240 mg every 2 weeks for 12 weeks. Nivolumab will be administered first, followed by carboplatin, followed by paclitaxel. * Cabiralizumab will be given IV at a dose of 4 mg/kg every 2 weeks for 12 weeks.

Group III: Arm A: Neoadjuvant chemo + nivolumab Active Control 6 Interventions

-Neoadjuvant chemotherapy consists of paclitaxel and carboplatin. Paclitaxel will be given intravenously (IV) at a dose of 80 mg/m\^2 on a weekly basis for 12 weeks. Carboplatin will be given IV at a dose of AUC 5 every 3 weeks for 12 weeks. Nivolumab will be given IV at a dose of 240 mg every 2 weeks for 12 weeks. Nivolumab will be administered first, followed by carboplatin, followed by paclitaxel.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a study using various mouse models of triple negative breast cancer (TNBC), the combination of nintedanib (an antiangiogenic drug) and paclitaxel (PTX) showed enhanced antitumor efficacy in both primary and metastatic settings, indicating a potential new treatment strategy for TNBC.

The triple combination of nintedanib, PTX, and a PD-L1 antibody demonstrated optimal efficacy in advanced metastatic models, suggesting that this combination could improve treatment outcomes for patients with TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic impact of Nintedanib with paclitaxel and/or a PD-L1 antibody in preclinical models of orthotopic primary or metastatic triple negative breast cancer. Reguera-Nuñez, E., Xu, P., Chow, A., et al.[2023]

In a study using patient-derived xenografts from nine chemotherapy-naïve triple-negative breast cancer (TNBC) samples, docetaxel and carboplatin were found to be effective as single agents, while doxorubicin showed low activity.

The combination of docetaxel and carboplatin was more effective than either drug alone, particularly in models without hereditary mutations, highlighting the potential for optimized treatment strategies in TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts. Martin, M., Ramos-Medina, R., Bernat, R., et al.[2021]

In a clinical trial involving 90 patients with triple negative breast cancer (TNBC), the optimal chemotherapy regimen combined carboplatin with standard dose-dense ACT, resulting in the lowest grade 3 or 4 toxicities and no delays or dose reductions for carboplatin.

The study identified reduced protein levels of androgen receptor and PD-L1 as potential indicators of treatment response, with Stage I patients showing a zero relapse rate, suggesting the effectiveness of the carboplatin-based regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective phase II clinical trial identifying the optimal regimen for carboplatin plus standard backbone of anthracycline and taxane-based chemotherapy in triple negative breast cancer. Hamm, C., Fifield, BA., Kay, A., et al.[2022]

In the IMpassion130 trial, the combination of atezolizumab and nab-paclitaxel (A + nP) significantly improved progression-free survival in patients with metastatic triple-negative breast cancer (mTNBC) without negatively impacting their health-related quality of life (HRQoL).

Patient-reported outcomes showed no significant differences in HRQoL or functioning between the A + nP and placebo plus nab-paclitaxel groups, indicating that the treatment did not worsen symptoms like fatigue or nausea, thus maintaining patients' day-to-day functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes from the phase III IMpassion130 trial of atezolizumab plus nab-paclitaxel in metastatic triple-negative breast cancer. Adams, S., Diéras, V., Barrios, CH., et al.[2022]

In a phase 3 trial involving 902 patients with metastatic triple-negative breast cancer, the combination of atezolizumab and nab-paclitaxel showed a median overall survival of 21.0 months compared to 18.7 months with placebo, although this difference was not statistically significant in the overall population.

For patients with PD-L1 immune cell-positive tumors, atezolizumab plus nab-paclitaxel demonstrated a significant overall survival benefit, with a median survival of 25.0 months versus 18.0 months for placebo, highlighting its potential as an important treatment option for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Schmid, P., Rugo, HS., Adams, S., et al.[2020]

In a study of 190 patients with stage I-III triple-negative breast cancer (TNBC), the neoadjuvant regimen of carboplatin and docetaxel (CbD) achieved a high pathologic complete response (pCR) rate of 55%, indicating effective tumor reduction before surgery.

The CbD regimen was well tolerated, with only 21% of patients experiencing grade 3 or 4 adverse events, suggesting it is a safe treatment option comparable to traditional chemotherapy combinations that include anthracyclines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts. Sharma, P., López-Tarruella, S., García-Saenz, JA., et al.[2022]

Citations

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Timing of nivolumab with neoadjuvant carboplatin and ... We aimed to investigate the activity of two differing schedules of neoadjuvant nivolumab initiation with 12 weeks of carboplatin and paclitaxel for this ...

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Articles Timing of nivolumab with neoadjuvant carboplatin ... Taxane and carboplatin have a favourable efficacy and toxicity profile, showing pathological complete response rates in patients with stage I–III triple- ...

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Immunotherapy for Triple-Negative Breast Cancer This review will analyze current immunotherapy strategies in TNBC, summarize the current landscape of clinical trials, review the results achieved, and shed ...

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NCT02309177 | Safety Study of Nivolumab With Nab- ... The purpose of this study is to assess safety of nab-paclitaxel based chemotherapy regimens administered prior to and/or in combination with nivolumab in ...