Neratinib in Combination With Ruxolitinib in Patients With mTNBC

Inclusion Criteria: * A patient will be considered for enrollment in this study if all the following criteria are met: 1. Female patients ≥18 years of age 2. Have a diagnosis of metastatic TNBC previously treated with standard anthracycline, cyclophosphamide, and taxane chemotherapy, unless there was a contraindication to doxorubicin, in which case prior treatment with this agent is not required. Note. TNBC defined as ER-negative tumors with ≤10% tumor nuclei immunoreactivity, or "ER Low Positive" as defined by the updated ASCO/CAP guidelines 2020. 3. Have not received more than 4 prior chemotherapy regimens for metastatic disease. Prior platinum and/or taxane therapy in the adjuvant or metastatic setting is permitted. Patients with more than 4 prior regimens may be allowed on study per physician discretion, if ECOG PS is 0-1. 4. Have locoregional (e.g., breast, chest wall, regional lymphatic) or pulmonary or hepatic metastatic disease that is amenable to core needle biopsy. If a research biopsy from a patient's metastatic disease cannot be safely obtained, a skin biopsy is permitted. If a skin biopsy cannot be safely obtained, patients may still be eligible, per physician discretion. 5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 6. Have adequate hematologic function, defined by: 1. Absolute neutrophil count (ANC) \>1500/µL 2. Platelet count ≥100,000/ µL 3. Hemoglobin ≥9 g/dL or ≥5.6 mmol/L 7. Have adequate liver function, defined by: 1. AST and ALT ≤2.5 x the upper limit of normal (ULN) or ≤5 x ULN in presence of liver metastases 2. Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels \>1.5 × ULN 8. Have adequate renal function, defined by: a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥30 mL/min 9. Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met: 10. Brain metastases which have been treated 11. Off-treatment with steroids before administration of the first dose of treatment 12. No ongoing requirement for dexamethasone or anti-epileptic drugs 13. No clinical or radiological evidence of progression of brain metastases 14. Patients must be accessible for treatment and follow-up. 15. All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry. Exclusion Criteria: * A patient will be ineligible for inclusion in this study any of the following criteria are met: 1. Has received a live vaccine or live-attenuated vaccine within 30 days of the first dose of study treatment. Administration of killed vaccines is allowed. 2. Has peripheral neuropathy ≥grade 2 3. Has completed previous radiotherapy for metastatic disease \<2 weeks prior to study treatment initiation 4. Has an active infection requiring systemic therapy 5. Has significant cardiovascular disease, such as: 1. History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass grafting within the last 6 months 2. Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV, or history of CHF NYHA class III or IV. 6. Has a known history of active tuberculosis 7. Women who are pregnant or lactating. All patients with reproductive potential must agree to use effective contraception from time of study entry until at least 3 months after the last administration of study drug. 8. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation such as: 1. severe impaired lung functions as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air 2. liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C). 9. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's full participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the Treating Physician. 10. Has received prior systemic anti-cancer therapy within 2 weeks prior to study treatment. 11. Has received investigational agents within 4 weeks prior to study treatment. Monoclonal antibody agents should have a 4-week (28 day) washout period. 12. Any other investigational or anti-cancer treatments while participating in this study 13. Any other active malignancy