A Phase II Study of Nivolumab in Combination With Cabozantinib for Metastatic Triple-negative Breast Cancer

Inclusion Criteria

• Participants must have histologically or cytologically confirmed invasive breast cancer, with metastatic disease. Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
• Estrogen-receptor and progesterone-receptor expression both 20%) have safety concerns, we will reassess the safety of collecting the research biopsies. Full review of all grade (including grade 1 and 2) may also prompt changes and will be reviewed by the study team. Exelixis may be consulted if necessary.
• Prior chemotherapy: Participants may have received 0-3 prior chemotherapeutic regimens for metastatic breast cancer and must have been off treatment with chemotherapy for at least 14 days prior to registration. Participants should also be adequately recovered from acute toxicities of prior treatment.
• Prior biologic therapy: Patients must have discontinued all biologic therapy at least 14 days prior to registration.
• Prior radiation therapy: Patients may have received prior radiation therapy in either the metastatic or early-stage setting. Radiation therapy must be completed per the following timelines:
• Radiotherapy to the thoracic cavity or abdomen within 4 weeks prior to registration.
• Radiotherapy to bone lesions within 2 weeks prior to registration.
• Radiotherapy to any other site within 4 weeks prior to registration.
• In all cases, there must be complete recovery and no ongoing complications from prior radiotherapy.
• The subject is ≥18 years old.
• ECOG (Eastern Cooperative Oncology Group) performance status ≤1(Karnofsky ≥60%, see Appendix A)
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/microliter (mcL)
• platelets ≥100,000/mcL
• hemoglobin ≥ 9 g/dl
• total bilirubin ≤1.5 × institutional upper limit of normal (ULN) (or 2.0 x ULN in patients with documented Gilbert's Syndrome)
• Aspartate aminotransferase (AST) / Alanine transaminase (ALT) ≤2.5 × institutional ULN or ≤ 3 × institutional ULN for participants with documented liver metastases
• creatinine 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment;
• Any history of congenital long QT syndrome;
• Any of the following within 6 months before the first dose of study treatment:
• unstable angina pectoris;
• clinically-significant cardiac arrhythmias;
• stroke (including transient ischemic attack (TIA), or other ischemic event);
• myocardial infarction;
• GI disorders particularly those associated with a high risk of perforation or fistula formation including:
• Tumors invading the GI tract, active peptic ulcer disease, active inflammatory bowel disease (eg, Crohn's disease), active diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction
• Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before randomization, Note: Complete healing of an intra-abdominal abscess must be confirmed prior to randomization
• Other clinically significant disorders that would preclude safe study participation;
• Corrected Fridericia's QT interval (QTcF) interval >500 msec Note: Three ECGs must be performed for eligibility determination. If the average of these three consecutive results for QTcF is ≤ 500 msec, the subject meets eligibility in this regard.
• Thromboembolic events requiring therapeutic anticoagulation. Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors), platelet inhibitors (eg, clopidogrel) are prohibited.

Note: Low-dose aspirin for cardioprotection (per local applicable guidelines) and low-dose low molecular weight heparin (LMWH) are permitted (in subjects who are on a stable