Tivozanib Hydrochloride in Combination With Paclitaxel Versus Placebo With Paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer

Inclusion Criteria:

- Locally recurrent or metastatic TNBC, defined as ER/PR <1%, HER2 0-1+, or 2+ with
negative FISH

- Measurable disease per RECIST version 1.1

- ECOG performance status of 0 or 1

- Confirmed available archival tumor tissue.

Exclusion Criteria:

- More than 1 prior systemic chemotherapy for treatment of locally recurrent or
metastatic breast cancer (neoadjuvant and adjuvant therapy is allowed provided the
subject did not progress within 12 months of taxane based therapy

- Prior treatment with VEGF pathway targeted agent

- Major surgery within 4 weeks or minor surgery or radiotherapy within 2 weeks of first
dose of study drug

- Known history of central nervous system metastasis (subjects with previously treated
(radiotherapy or surgery) brain metastasis that have been stable off steroids or
enzyme-inducing antiepileptic drugs for at least 3 months following prior treatment
may be enrolled)

- Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or
coagulation disorders

- Significant serum chemistry or urinalysis abnormalities

- Significant cardiovascular disease, including: uncontrolled hypertension; myocardial
infarction or unstable angina within 6 months prior to administration of first dose of
study drug; and symptomatic left ventricular dysfunction or baseline left ventricular
ejection fraction (LVEF) by multigated acquisition scan (MUGA) or ECHO.

- Severe peripheral neuropathy ≥ Grade 2

- Currently active second primary malignancy