This phase II trial studies how well nab-paclitaxel, durvalumab, and tremelimumab with or without personalized synthetic long peptide vaccine (neoantigen vaccine) works in treating patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. It is not yet known whether giving nab-paclitaxel, durvalumab, and tremelimumab with or without neoantigen vaccine will work better in treating patients with triple negative breast cancer.
Patients must have a histologically confirmed diagnosis of metastatic invasive triple negative breast cancer. Patients with clinical and/or radiologic suspicion of metastatic TNBC can be consented prior to this confirmation.
Estrogen receptor (ER) and progesterone receptor (PR) less than Allred score of 3 OR less than 1% positive staining cells in the invasive component of the tumor.
HER2 negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+.
PD-L1 negative by a Clinical Laboratory Improvement Act (CLIA) approved laboratory using compatible assays appropriate for treatment decisions.
Patients who are not considered to be candidates for carboplatin + gemcitabine for first line therapy of their metastatic triple negative breast cancer are not eligible.
Patients who have had chemotherapy, radiotherapy (to more than 30% of the bone marrow), or biologic therapy within 30 days (42 days for nitrosoureas or mitomycin C) prior to entering the study.
Patients who have received prior immunotherapy for metastatic disease.
Patients who have not recovered from grade >= 2 adverse events due to prior anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
Parallel
Biopsy Procedure
Procedure/SurgeryUndergo tumor biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood and urine sample collection
Carboplatin
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT scan
Durvalumab
Biological/VaccineGiven IV
Gemcitabine Hydrochloride
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Nab-paclitaxel
DrugGiven IV
Personalized Synthetic Long Peptide Vaccine
Biological/VaccineGiven SC
Poly ICLC
DrugGiven SC
Sacituzumab Govitecan
Biological/VaccineGiven IV
Tremelimumab
Biological/VaccineGiven IV
Progression-free survival (PFS)
The median PFS in each arm and their 80% confidence intervals will be assessed using Kaplan-Meier product limit methods and compared by log-rank test.
Incidence of adverse events
Will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. The number and percentage of subjects experiencing each type of adverse event will be tabulated by severity, and relationship to treatment. If appropriate, confidence intervals will be used to characterize the precision of the estimate.
Clinical response rate
Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be assessed and their 95% confidence intervals will be calculated.
Clinical benefit rate (complete response, partial response, stable disease)
Will be assessed by RECIST 1.1. Will be assessed and their 95% confidence intervals will be calculated.
Overall survival (OS)
The median OS and 95% confidence interval will also be assessed using Kaplan-Meier product limit methods and compared by log-rank test.
Immune response
Immunogenicity biomarkers in both tumor tissues and peripheral blood will be summarized using descriptive statistics at each time point. The differences over time as well as the between-group differences will be compared using linear mixed model for repeated measurement data, followed by ad-hoc multiple comparisons for the specific differences of interest. The association between clinical response and baseline biomarkers (tumor infiltrating lymphocyte \[TIL\] percentage, expression of PD-L1 on TILs and tumor, triple negative breast cancer subtype as determined by gene expression, immune signature as determined by gene expression, mutational landscape, presence and phenotype of neoantigen-specific T cells, etc.) will also be explored by comparing the differences in theses biomarkers between responders versus non-responders using t-test, Mann-Whitney rank-sum test, or Fisher's exact test as appropriate.
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