Nivolumab + Chemotherapy for Triple-negative Breast Cancer

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

15 Participants Needed

Trial Summary

What is the purpose of this trial?

Prior to Amendment #7: The hypothesis of this study is that the combination of cabiralizumab and nivolumab with neoadjuvant chemotherapy will decrease tumor associated macrophages (TAMs) and increase tumor infiltrating lymphocytes (TIL) compared to neoadjuvant chemotherapy plus nivolumab in patients with early stage triple-negative breast cancer (TNBC) and improve clinical outcomes. As of Amendment #7 IRB approved 10/13/2022: The study will no longer enroll to Arm B. Cabiralizumab will no longer be given. The hypothesis of this study is that on-treatment tumor associated macrophages (TAMs) and tumor infiltrating lymphocytes (TILs) will improve (reduced TAMs, increased TILs) following neoadjuvant nivolumab with chemotherapy.

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.

What data supports the effectiveness of the drug Nivolumab + Chemotherapy for Triple-negative Breast Cancer?

Research shows that adding carboplatin to chemotherapy for triple-negative breast cancer (TNBC) has been effective, with some studies indicating a reduction in relapse rates. Additionally, combining paclitaxel with other drugs has shown benefits in treating TNBC, suggesting potential effectiveness of this combination. ^{1 2 3 4 5}

Is the combination of Nivolumab and chemotherapy safe for treating triple-negative breast cancer?

The combination of chemotherapy drugs like carboplatin and paclitaxel has been studied for safety in treating triple-negative breast cancer, showing manageable side effects such as myelosuppression (low blood cell counts) and neurotoxicity (nerve damage). While specific data on Nivolumab combined with these drugs is not provided, similar immunotherapy combinations have shown promising safety profiles in clinical trials. ^{1 6 7 8 9}

What makes the drug combination of Nivolumab, Carboplatin, and Paclitaxel unique for treating triple-negative breast cancer?

This drug combination is unique because it includes Nivolumab, an immunotherapy that helps the immune system attack cancer cells, alongside Carboplatin and Paclitaxel, which are chemotherapy drugs. This approach combines the immune-boosting effects of Nivolumab with the cancer-killing effects of chemotherapy, potentially offering a new strategy for treating triple-negative breast cancer, which currently lacks targeted therapies. ^{1 2 4 10 11}

Research Team

Andrew Davis, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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 18 years old or older.

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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 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]

References

1. United States 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Weekly Paclitaxel and Carboplatin Plus Bevacizumab as First-Line Treatment of Metastatic Triple-Negative Breast Cancer. A Multicenter Phase II Trial by the Hellenic Oncology Research Group. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial. [2022]

4. England 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts. [2021]

7. England 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. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin in early triple-negative breast cancer: a single-arm phase II trial. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Feasibility and toxicity of weekly Paclitaxel-Carboplatin in 131 patients with pretreated and non-pretreated solid tumors. [2022]

10. England pubmed.ncbi.nlm.nih.gov

First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. [2021]

11. England 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. [2023]