A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study)

Inclusion Criteria:

- Histologically or cytologically confirmed carcinoma of the breast

- Locally advanced breast cancer that is not amenable to curative radiation or surgical
cure and/or metastatic disease appropriate for systemic single cytotoxic chemotherapy

- Documentation of a deleterious, suspected deleterious, or pathogenic germline BRCA1 or
BRCA2 mutation from Myriad Genetics or other laboratory approved by the Sponsor

- No more than 3 prior chemotherapy-inclusive regimens for locally advanced and/or
metastatic disease (no limit on prior hormonal therapies or targeted anticancer
therapies such as mechanistic target of rapamycin (mTOR) or CDK4/6 inhibitors,
immune-oncology agents, tyrosine kinase inhibitors, or monoclonal antibodies against
CTL4 or VEGF)

- Prior treatment with a taxane and/or anthracycline in the neoadjuvant, adjuvant,
locally advanced, or metastatic setting unless medically contraindicated

- Have measurable or non-measurable, evaluable disease by the revised response
evaluation criteria in solid tumors (RECIST) v.1.1

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

Exclusion Criteria:

- First-line locally advanced and/or metastatic breast cancer with no prior adjuvant
chemotherapy unless the Investigator determines that one of the 4 cytotoxic
chemotherapy agents in the control arm would otherwise be offered to the subject

- Prior treatment with a PARP inhibitor (not including iniparib)

- Not a candidate for treatment with at least 1 of the treatments of protocol-specific
physician's choice (ie, capecitabine, eribulin, gemcitabine, vinorelbine)

- Subjects who had objective disease progression while receiving platinum chemotherapy
administered for locally advanced or metastatic disease; subjects who received
low-dose platinum therapy administered in combination with radiation therapy are not
excluded

- Subjects who have received platinum in the adjuvant or neoadjuvant setting are
eligible; however, subjects may not have relapsed within 6 months of the last dose of
prior platinum therapy

- Cytotoxic chemotherapy within 14 days before randomization

- Radiation or anti-hormonal therapy or other targeted anticancer therapy within 14 days
before randomization

- HER2 positive breast cancer

- Active inflammatory breast cancer

- CNS metastases

- Exception: Adequately treated brain metastases documented by baseline CT or MRI
scan that has not progressed since previous scans and that does not require
corticosteroids (except prednisone ≤ 5 mg/day or equivalent) for management of
CNS symptoms. A repeat CT or MRI following the identification of CNS metastases
(obtained at least 2 weeks after definitive therapy) must document adequately
treated brain metastases.

- Subjects with leptomeningeal carcinomatosis are not permitted

- Prior malignancy except for any of the following:

- Prior BRCA-associated cancer as long as there is no current evidence of the
cancer

- Carcinoma in situ or non-melanoma skin cancer

- A cancer diagnosed and definitively treated ≥ 5 years before randomization with
no subsequent evidence of recurrence

- Known to be human immunodeficiency virus positive

- Known active hepatitis C virus, or known active hepatitis B virus

- Known hypersensitivity to any of the components of talazoparib