Sitravatinib in Metastatic Breast Cancer

Inclusion Criteria:

* Women or men age 18 and older
* Metastatic or locally advanced inoperable breast cancer (beyond curative management) that is measurable according to RECIST 1.1 criteria. Note: Patients with bone-only disease are eligible if there is at least 1 lytic lesion that can be followed for response.
* Tumor is estrogen receptor (ER) negative and progesterone receptor (PR) negative per the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) Guidelines of 2010.
* Tumor is HER2neu negative per ASCO/CAP Guidelines of 2018
* Patient has archival tissue from metastatic or locally advanced breast cancer for the analysis of PTPN12 status
* At least one prior line of chemotherapy with or without a PD-L1 or PD-1 antibody in the metastatic setting
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
* Normal organ and marrow function as defined below:

  * Absolute neutrophil count \> 1000/mcL
  * Hemoglobin \> 11 g/dL
  * Platelets \> 100,000/mcL
  * Total bilirubin \< 1.5 X normal institutional limits
  * Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \< 2.5 X institutional ULN or ≤ 5.0 × ULN for patients with documented liver metastases.
  * Creatinine within normal institutional limits
  * Creatinine clearance ≥ 30 mL/min
  * Normal left ventricular ejection (LVEF) function defined as normal left ventricular wall motion and ejection fraction of ≥ 50%.
* If patient has brain metastasis, documented treatment and stability for at least 30 days by scans and off steroids at the time of enrollment
* Women of child bearing age and actively menstruating must have a negative pregnancy test prior to starting study treatment.
* If sexually active in a way that could lead to pregnancy, participant must agree to use a highly effective method of birth control starting at the time of informed consent and continuing throughout the study and for at least 3 months after the final dose of sitravatinib.
* Ability to understand and the willingness to give informed consent

Exclusion Criteria:

* Uncontrolled hypertension defined as systolic blood pressure \> 150 and/or diastolic blood pressure \> 100, on two or more occasions within 30 days prior to enrollment.
* Imaging suggestive of Lymphangitic carcinomatosis in the lung, or use of home oxygen
* Untreated brain metastases.
* Women who are pregnant or nursing
* Concurrent metastatic disease of another tumor type
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of sitravatinib
* History of stroke, pulmonary embolus (PE), or myocardial infarction (MI)
* Known proteinuria of ≥ 2 g urinary protein/24 h
* HIV-positive participants
* History of Hepatitis C or Hepatitis B infection
* History of congestive heart failure (CHF), and/or LVEF less than 50%
* Concurrent use of medications that prolong QTc (listed in Section 9, Table 11). These medications need to be discontinued at least 2 weeks prior to starting study treatment.
* Concurrent medical condition that, in the sole judgment of the principal investigator, would make the patient inappropriate for trial participation.