Neoadjuvant Nivolumab and Chemotherapy in Patients With L... | NCT04331067

Name	Class
Bristol-Myers Squibb	INDUSTRY

Label	Type	Description	Intervention Names
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.

Name	Type	Description	Arm Group Labels	Other Names
Paclitaxel	Drug	-Given standard of care	Arm A: Neoadjuvant chemo + nivolumab Arm B: Neoadjuvant chemo + nivolumab + cabiralizumab Unrandomized Arm: Neoadjuvant Chemo + Nivolumab

Measure	Description	Time Frame
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)

Measure	Description	Time Frame
Pathological Complete Response (pCR)	-A pathologic complete response (pCR) is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.	At time of surgery (average of 12 weeks)
Recurrence-free Survival (RFS)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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
- Albumin ≥ 3 g/dL
- INR and aPTT <1.5 x IULN (This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose).
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
Women must not be breastfeeding.
WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) and for a total of 5 months post-treatment completion.
Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Consent for fresh pre-treatment, on-treatment, biopsy samples at acceptable clinical risk, as judged by the investigator.
Participants must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing

Exclusion Criteria:

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
  - Rash must cover less than 10% of body surface area (BSA)
  - Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
  - No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
Uncontrolled or significant cardiovascular disease
History of any chronic hepatitis as evidenced by the following:
- Positive test for hepatitis B surface antigen
- Positive test for qualitative hepatitis C viral load (by polymerase chain reaction [PCR]).
Positive test for latent tuberculosis (TB) at screening (e.g. T-SPOT or Quantiferon test) or evidence of active TB.
Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study with the exception of the planned breast cancer surgery that is part of the trial design. Participants must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment.
Any uncontrolled medical condition which, in the opinion of the Investigator, would pose a risk to participant safety or interfere with study participation or interpretation of individual participant results.
Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1.
- Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.
- The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. The use of replacement doses of prednisone or other corticosteroid for adrenocortical insufficiency is allowed
- Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
Evidence of coagulopathy or bleeding diathesis.
Ascites needing paracentesis or medical management.
Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must have:
- A stable regimen of highly active anti-retroviral therapy (HAART)
- No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
- A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests

Name	Affiliation	Role
Andrew Davis, M.D.	Washington University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Washington University School of Medicine		St Louis	Missouri	63110	United States

Label	URL
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine	View source

ID	Title	Description
FG000	Arm A: Neoadjuvant Chemo + Nivolumab	-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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jul 27, 2022

ID	Title	Description
BG000	Arm A: Neoadjuvant Chemo + Nivolumab	-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.
BG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.
BG002	Unrandomized Arm: Neoadjuvant Chemo + Nivolumab	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.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0006 BG0016 BG0023 BG00315

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Arm A and Unrandomized Arm were analyzed together as the treatment received was the same. There were 2 participants with missing data in Arm A/Unrandomized Arm and 2 participants with missing data in Arm B and these participants were not included in the analysis.

Posted

Mean

Standard Deviation

percent change

Baseline and week 5

ID	Title	Description
OG000	Arm A and Unrandomized Arm: Neoadjuvant Chemo + Nivolumab	-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.
OG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.

Units	Counts
Participants	OG0007 OG0014

Title

Denominators

Categories

Title	Measurements
	OG00095.2± 121 OG0011.63± 82.5

Primary

Percent Change in Tumor Associated Macrophages (TAMs)

Arm A and Unrandomized Arm were analyzed together as the treatment received was the same. There were 3 participants with missing data in Arm A/Unrandomized Arm and 3 participants with missing data in Arm B and these participants were not included in the analysis.

Posted

Mean

Standard Deviation

percent change

Baseline and week 5

ID	Title	Description
OG000	Arm A and Unrandomized Arm: Neoadjuvant Chemo + Nivolumab	-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.
OG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.

Primary

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).

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Arm A: Neoadjuvant Chemo + Nivolumab	-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.
OG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.

Secondary

Pathological Complete Response (pCR)

-A pathologic complete response (pCR) is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.

1 participant in Arm A and 1 participant in Arm B did not have surgery.

Posted

Count of Participants

Participants

At time of surgery (average of 12 weeks)

ID	Title	Description
OG000	Arm A: Neoadjuvant Chemo + Nivolumab	-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.
OG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.

Secondary

Recurrence-free Survival (RFS)

-RFS is defined from time of surgery to the earliest time of recurrence, time to development of a second cancer, or time to death from any cause.

Not Posted

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

Participants

Secondary

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

Treatment related means either possibly, probably, or definitely related to nivolumab

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Arm A: Neoadjuvant Chemo + Nivolumab	-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.
OG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.

Secondary

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

Treatment related means either possibly, probably, or definitely related to carboplatin

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Arm A: Neoadjuvant Chemo + Nivolumab	-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.
OG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.

Secondary

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

Treatment related means either possibly, probably, or definitely related to paclitaxel

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Arm A: Neoadjuvant Chemo + Nivolumab	-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.
OG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.

Secondary

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

Treatment related means either possibly, probably, or definitely related to cabiralizumab

This outcome measure is only for Arm B as that arm is the only arm that received cabiralizumab.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Arm A: Neoadjuvant Chemo + Nivolumab	-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.
OG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.

Secondary

Compare the Percent Change of Tumor Associated Macrophages (TAMs) Between Participants Who Achieve pCR Versus Those Who do Not

-A pathologic complete response (pCR) is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.

Arm A and Unrandomized Arm were analyzed together as the treatment received was the same. There were 2 participants with missing data in Arm A/Unrandomized Arm and 3 participants with missing data in Arm B and these participants were not included in the analysis.

Posted

Mean

Standard Deviation

percent change

At time of surgery (average of 12 weeks)

ID	Title	Description
OG000	Arm A and Unrandomized Arm: Neoadjuvant Chemo + Nivolumab	-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.
OG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.

Secondary

Compare the Percent Change of Tumor Infiltrating Lymphocytes (TILs) Between Participants Who Achieve pCR Versus Those Who do Not

Stromal TIL score is defined as the percentage of tumor stroma area that was occupied by mononuclear inflammatory cells.
A pathologic complete response (pCR) is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.

Arm A and Unrandomized Arm were analyzed together as the treatment received was the same. There were 3 participants with missing data in Arm A/Unrandomized Arm and 4 participants with missing data in Arm B and these participants were not included in the analysis.

Posted

Mean

Standard Deviation

percent change

At time of surgery (average of 12 weeks)

ID	Title	Description
OG000	Arm A and Unrandomized Arm: Neoadjuvant Chemo + Nivolumab	-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.
OG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0006 affected6 at risk EG0015 affected6 at risk EG0023 affected3 at risk
Lymph node pain	Blood and lymphatic system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Supraventricular tachycardia	Cardiac disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Adrenal insufficiency	Endocrine disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected3 at risk
Diabetes	Endocrine disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Hypoparathyroidism	Endocrine disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Hypothyroidism	Endocrine disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Blurred vision	Eye disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Eye pain	Eye disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Periorbital edema	Eye disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0014 affected6 at risk EG0020 affected3 at risk
Photophobia	Eye disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Uveitis	Eye disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Watering eyes	Eye disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0013 affected6 at risk EG0020 affected3 at risk
Abdominal pain	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Constipation	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0021 affected3 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0013 affected6 at risk EG0023 affected3 at risk
Dry mouth	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG0021 affected3 at risk
Dyspepsia	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0021 affected3 at risk
Dysphagia	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Gas pain	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Gastrointestinal pain	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Mucositis oral	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0015 affected6 at risk EG0021 affected3 at risk
Nausea	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0005 affected6 at risk EG0015 affected6 at risk EG0021 affected3 at risk
Vomiting	Gastrointestinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Chills	General disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Edema limbs	General disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0013 affected6 at risk EG0020 affected3 at risk
Edema trunk	General disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Fatigue	General disorders	CTCAE (Unspecified)	Systematic Assessment	EG0006 affected6 at risk EG0014 affected6 at risk EG0023 affected3 at risk
Fever	General disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0013 affected6 at risk EG0020 affected3 at risk
Flu like symptoms	General disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Generalized body aches	General disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Localized edema	General disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Neck edema	General disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Non-cardiac chest pain	General disorders	CTCAE (Unspecified)	Systematic Assessment	EG0003 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Pain	General disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected3 at risk
Allergic reaction	Immune system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Bronchitis	Infections and infestations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Cold symptoms	Infections and infestations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Conjunctivitis	Infections and infestations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Eye infection	Infections and infestations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected3 at risk
Folliculitis	Infections and infestations	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected3 at risk
Paronychia	Infections and infestations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected3 at risk
Thrush	Infections and infestations	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Urinary tract infection	Infections and infestations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Fall	Injury, poisoning and procedural complications	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Infusion related reaction	Injury, poisoning and procedural complications	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Seroma	Injury, poisoning and procedural complications	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Alanine aminotransferase increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0004 affected6 at risk EG0016 affected6 at risk EG0021 affected3 at risk
Alkaline phosphatase increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0003 affected6 at risk EG0015 affected6 at risk EG0020 affected3 at risk
Aspartate aminotransferase increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0016 affected6 at risk EG0021 affected3 at risk
Blood lactate dehydrogenase increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0004 affected6 at risk EG0016 affected6 at risk EG0020 affected3 at risk
CPK increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0016 affected6 at risk EG0020 affected3 at risk
Cardiac troponin I increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Cardiac troponin T increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Cholesterol high	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Creatinine increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Fibrinogen decreased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Haptoglobin decreased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
INR increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Lipase increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0015 affected6 at risk EG0020 affected3 at risk
Lymphocyte count decreased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0003 affected6 at risk EG0015 affected6 at risk EG0022 affected3 at risk
Lymphocyte count increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected3 at risk
Neutrophil count decreased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0003 affected6 at risk EG0016 affected6 at risk EG0023 affected3 at risk
Platelet count decreased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0004 affected6 at risk EG0015 affected6 at risk EG0021 affected3 at risk
Thyroid stimulating hormone increased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Weight gain	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Weight loss	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG0021 affected3 at risk
White blood cell count decreased	Investigations	CTCAE (Unspecified)	Systematic Assessment	EG0005 affected6 at risk EG0016 affected6 at risk EG0023 affected3 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0013 affected6 at risk EG0021 affected3 at risk
Dehydration	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Hypercalcemia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0013 affected6 at risk EG0021 affected3 at risk
Hyperkalemia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Hypernatremia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Hypertriglyceridemia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Hyperuricemia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Hypocalcemia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0013 affected6 at risk EG0020 affected3 at risk
Hypoglycemia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0013 affected6 at risk EG0021 affected3 at risk
Hypomagenesemia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG0021 affected3 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0012 affected6 at risk EG0021 affected3 at risk
Hypophosphatemia	Metabolism and nutrition disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0013 affected6 at risk EG0020 affected3 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Arthritis	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Back aches	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Back pain	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Back spasms	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Bilateral rib pain	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Bone pain	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0013 affected6 at risk EG0020 affected3 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Muscle cramp	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Muscle soreness	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Myalgia	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Shoulder pain	Musculoskeletal and connective tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Dizziness	Nervous system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0004 affected6 at risk EG0014 affected6 at risk EG0021 affected3 at risk
Dysgeusia	Nervous system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0013 affected6 at risk EG0022 affected3 at risk
Encephalopathy	Nervous system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Headache	Nervous system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0004 affected6 at risk EG0012 affected6 at risk EG0022 affected3 at risk
Jitters	Nervous system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Memory impairment	Nervous system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Peripheral motor neuropathy	Nervous system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Peripheral sensory neuropathy	Nervous system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0003 affected6 at risk EG0015 affected6 at risk EG0023 affected3 at risk
Syncope	Nervous system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Tremor	Nervous system disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Agitation	Psychiatric disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Altered mental state	Psychiatric disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Depression	Psychiatric disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Insomnia	Psychiatric disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0013 affected6 at risk EG0021 affected3 at risk
Mania	Psychiatric disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Acute kidney injury	Renal and urinary disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Glucosuria	Renal and urinary disorders	CTCAE (Unspecified)	Systematic Assessment	EG0003 affected6 at risk EG0013 affected6 at risk EG0020 affected3 at risk
Hematuria	Renal and urinary disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0013 affected6 at risk EG0020 affected3 at risk
Proteinuria	Renal and urinary disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0013 affected6 at risk EG0021 affected3 at risk
Urinary urgency	Renal and urinary disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Areola pain	Reproductive system and breast disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Breast edema	Reproductive system and breast disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Breast pain	Reproductive system and breast disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Irregular menstruation	Reproductive system and breast disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0004 affected6 at risk EG0011 affected6 at risk EG0022 affected3 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0003 affected6 at risk EG0013 affected6 at risk EG0022 affected3 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected3 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Sore throat	Respiratory, thoracic and mediastinal disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected3 at risk
Alopecia	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0004 affected6 at risk EG0014 affected6 at risk EG0022 affected3 at risk
Dermatitis radiation	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Dry skin	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected3 at risk
Flat, lacy rash	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Hyperhydrosis	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected3 at risk
Macular rash	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk
Photosensitivity	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Pruritus	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0003 affected6 at risk EG0013 affected6 at risk EG0022 affected3 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected3 at risk
Skin pain on chest and arms	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Skin ulceration	Skin and subcutaneous tissue disorders	CTCAE (Unspecified)	Systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG0020 affected3 at risk
Hot flashes	Vascular disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0021 affected3 at risk
Hypertension	Vascular disorders	CTCAE (Unspecified)	Systematic Assessment	EG0003 affected6 at risk EG0014 affected6 at risk EG0020 affected3 at risk
Hypotension	Vascular disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0020 affected3 at risk
Thromboembolic event	Vascular disorders	CTCAE (Unspecified)	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0020 affected3 at risk

ID	Term
D001943	Breast Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D056831	Coordination Complexes
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D013048	Specimen Handling
D019411	Clinical Laboratory Techniques
D019937	Diagnostic Techniques and Procedures
D003933	Diagnosis
D011677	Punctures
D013514	Surgical Procedures, Operative
D008919	Investigative Techniques

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A: Neoadjuvant Chemo + Nivolumab	-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.	1	6	1	6	6	6
EG001	Arm B: Neoadjuvant Chemo + Nivolumab + Cabiralizumab	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.	1	6	3	6	6	6
EG002	Unrandomized Arm: Neoadjuvant Chemo + Nivolumab	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.	0	3	0	3	3	3

ID	Term
D017239	Paclitaxel
D016190	Carboplatin
D000077594	Nivolumab
C000722457	cabiralizumab
D001800	Blood Specimen Collection