This is an open-label Phase 3 study to see if ANG1005 can prolong survival compared to a Physician Best Choice control in HER2-negative breast cancer patients with newly diagnosed leptomeningeal disease and previously treated brain metastases.

Inclusion Criteria:

1. ≥ 18 years old
2. HER2-negative breast cancer
3. At least 2 months of expected survival
4. Newly diagnosed leptomeningeal carcinomatosis
5. Documented history of brain metastasis that has been previously treated with radiation therapy
6. Neurologically stable
7. Eastern Cooperative Oncology Group performance status grade ≤2
8. Adequate laboratory test results prior to first dose
9. Patients who are fertile must agree to remain abstinent or use reliable method of birth control

Exclusion Criteria:

1. Any prior treatment for leptomeningeal carcinomatosis, except emergency radiotherapy or shunt
2. Prior treatment with ANG1005
3. Patients who have not had radiotherapy for their brain metastases
4. Evidence of symptomatic intracranial hemorrhage or increased intracranial pressure
5. Patients for whom intrathecal therapy is the most appropriate therapy for leptomeningeal disease
6. Pregnancy or lactation and patients planning to be pregnant during the study
7. Peripheral neuropathy > Grade 2
8. Evidence of severe or uncontrolled diseases
9. Presence of an infection including abscess or fistulae, or known infection with hepatitis B or C or HIV
10. History of interstitial lung disease
11. Severe conduction disturbance
12. Central nervous system disease requiring immediate neurosurgical intervention
13. Known allergy to paclitaxel or any of its components
14. Contra-indication for contrast-enhanced MRI