A Phase 2 Randomized, Double-Blind, Placebo-Controlled, 2-Arm, Multi-center Study Comparing Tivozanib Hydrochloride in Combination With Paclitaxel Versus Placebo in Combination With Paclitaxel in the Treatment of Subjects With Locally Recurrent and/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:

- Any prior systemic chemotherapy for treatment of locally recurrent or metastatic
breast cancer (neoadjuvant and adjuvant therapy is allowed provided the subject did
not progress and that there is >6 months (>12 months for taxane based therapy) since
end of treatment and first dose of study drug and any toxicities have resolved to ≤
Grade 1)

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

- Untreated central nervous system metastases (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