Neoadjuvant Nivolumab and Chemotherapy in Patients With Localized Triple-negative Breast Cancer

NCT04331067 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: 202007016
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Percent Change in Tumor Infiltrating Lymphocytes (TILs)

  -Stromal TIL score is defined as the percentage of tumor stroma area that was occupied by mononuclear inflammatory cells.

  Baseline and week 5

• Percent Change in Tumor Associated Macrophages (TAMs)

  Baseline and week 5

• Safety of the Regimen as Measured by Incidence of Adverse Events (Safety lead-in Only)

  Safety lead-in consists of the first 12 patients treated on the study (Arm A and Arm B).

  From start of treatment through 100 days after last day of study treatment or surgery whichever occurs first (approximately 16 weeks)

Secondary Outcomes (8)

• Pathological Complete Response (pCR)

  At time of surgery (average of 12 weeks)

• Recurrence-free Survival (RFS)

  Through completion of follow-up (estimated to be 3 years and 12 weeks)

• Adverse Events Measured by Number of Participants With Nivolumab Related Grade 3 or Higher Adverse Events

  From start of treatment through 100 days after last infusion of study treatment or surgery whichever occurs first (approximately 16 weeks)

• Adverse Events Measured by Number of Participants With Carboplain Related Grade 3 or Higher Adverse Events

  From start of treatment through 100 days after last infusion of study treatment or surgery whichever occurs first (approximately 16 weeks)

• Adverse Events Measured by Number of Participants With Paclitaxel Related Grade 3 or Higher Adverse Events

  From start of treatment through 100 days after last infusion of study treatment or surgery whichever occurs first (approximately 16 weeks)

Study Arms (3)

Arm A: Neoadjuvant chemo + nivolumab

ACTIVE COMPARATOR

-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.

Drug: Paclitaxel; Drug: Carboplatin; Biological: Nivolumab; Procedure: Tumor biopsy; Procedure: Bone marrow; Procedure: Blood draw

Arm B: Neoadjuvant chemo + nivolumab + cabiralizumab

EXPERIMENTAL

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.

Drug: Paclitaxel; Drug: Carboplatin; Biological: Nivolumab; Biological: Cabiralizumab; Procedure: Tumor biopsy; Procedure: Bone marrow; Procedure: Blood draw

Unrandomized Arm: Neoadjuvant Chemo + Nivolumab

EXPERIMENTAL

* 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.

Drug: Paclitaxel; Drug: Carboplatin; Biological: Nivolumab; Procedure: Tumor biopsy; Procedure: Bone marrow; Procedure: Blood draw

Interventions

Paclitaxel DRUG

-Given standard of care

Also known as: Taxol

Arm A: Neoadjuvant chemo + nivolumab; Arm B: Neoadjuvant chemo + nivolumab + cabiralizumab; Unrandomized Arm: Neoadjuvant Chemo + Nivolumab

Carboplatin DRUG

-Given standard of care

Also known as: Paraplatin

Arm A: Neoadjuvant chemo + nivolumab; Arm B: Neoadjuvant chemo + nivolumab + cabiralizumab; Unrandomized Arm: Neoadjuvant Chemo + Nivolumab

Nivolumab BIOLOGICAL

-Given standard of care

Also known as: Opdivo, BMS-936558

Arm A: Neoadjuvant chemo + nivolumab; Arm B: Neoadjuvant chemo + nivolumab + cabiralizumab; Unrandomized Arm: Neoadjuvant Chemo + Nivolumab

Cabiralizumab BIOLOGICAL

-Will be provided by Bristol Myers Squibb

Also known as: BMS-986227

Arm B: Neoadjuvant chemo + nivolumab + cabiralizumab

Tumor biopsy PROCEDURE

-Baseline, week 5, surgery, and at time of relapse (optional)

Arm A: Neoadjuvant chemo + nivolumab; Arm B: Neoadjuvant chemo + nivolumab + cabiralizumab; Unrandomized Arm: Neoadjuvant Chemo + Nivolumab

Bone marrow PROCEDURE

-Time of port placement (baseline), time of surgery, and time of recurrence (optional)

Arm A: Neoadjuvant chemo + nivolumab; Arm B: Neoadjuvant chemo + nivolumab + cabiralizumab; Unrandomized Arm: Neoadjuvant Chemo + Nivolumab

Blood draw PROCEDURE

-Baseline, week 5, prior to surgery , post-surgery follow-up (typically 3-4 weeks post-surgery), and disease progression (optional)

Arm A: Neoadjuvant chemo + nivolumab; Arm B: Neoadjuvant chemo + nivolumab + cabiralizumab; Unrandomized Arm: Neoadjuvant Chemo + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed newly diagnosed ER-/HER2- breast cancer. ER and PR \< Allred score of 3 or \< 1% positive staining cells in the invasive component of the tumor. HER2 negative by FISH or IHC staining 0 or 1+ according to NCCN guidelines.
• Clinical stage II or III (by AJCC 8th edition at least T2, any N, M0 or if N+ then any T) breast cancer eligible for neoadjuvant chemotherapy with complete surgical excision of the breast cancer after neoadjuvant therapy as the treatment goal.
• Tumor size at least 2 cm in one dimension by clinical or radiographic exam (WHO criteria). Patients with histologically confirmed or clinically palpable lymph nodes may be enrolled regardless of tumor size. A palpable mass is not required as long as the mass is at least 2 cm in one dimension by radiographic exam. 2D measurements should be completed during screening if available.
• No prior therapy for this disease
• At least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Normal bone marrow and organ function as defined below:
• Leukocytes ≥ 2,000/mcL (stable off any growth factor within 4 weeks of first study treatment administration)
• Absolute neutrophil count ≥ 1,500/mcL (stable off any growth factor within 4 weeks of first study treatment administration)
• Platelets ≥ 100,000/mcL (stable off any growth factor within 4 weeks of first study treatment administration)
• Hemoglobin ≥8.5 g/dl (transfusion to achieve this level is not permitted within 2 weeks of first study treatment administration)
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) (except participants with Gilbert's Syndrome who must have normal direct bilirubin)
• AST(SGOT)/ALT(SGPT) ≤ 2.0 x IULN
• Alkaline phosphatase \<2.5 x ULN
• Serum creatinine \< 1.5 x ULN or creatinine clearance \> 40 mL/min by Cockcroft-Gault

You may not qualify if:

• Prior treatment with immunotherapy for cancer
• Known metastatic disease
• Known invasive cancer in contralateral breast
• Patients with a previous history of non-breast malignancy are eligible only if they meet the following criteria for a cancer survivor:
• Has undergone potentially curative therapy for all prior malignancies AND
• Has been considered disease-free for at least 1 year (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix.
• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, carboplatin, nivolumab, or other agents used in the study. Patients who have received multiple blood transfusions.
• Evidence of uncontrolled ongoing or active infection, requiring parenteral anti-bacterial, anti-viral, or anti-fungal therapy ≤ 7 days prior to administration of study treatment. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
• Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease (Crohn's disease and ulcerative colitis), vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis.
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
• Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
• Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
• Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Paclitaxel; Carboplatin; Nivolumab; cabiralizumab; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Andrew Davis, M.D.
• Organization: Washington University School of Medicine

aadavis@wustl.edu

314-273-3581

Study Officials

• Andrew Davis, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 2, 2020
• Study Start: November 19, 2020
• Primary Completion: March 20, 2023
• Study Completion (Estimated): July 11, 2026
• Last Updated: May 6, 2026
• Results First Posted: May 16, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)