The Study Evaluating Efficacy And Tolerability Of Veliparib in Combination With Temozolomide or In Combination With Carboplatin and Paclitaxel Versus Placebo in Subjects With BRCA1 and BRCA2 Mutation and Metastatic Breast Cancer

Subjects will be randomized in a 1:1:1 ratio to one of the three treatment groups. The safety
of each treatment group will be assessed by evaluating study drug exposure, adverse events,
serious adverse events, all deaths, changes in laboratory determinations, and vital sign
parameters. The Clinical Benefit Rate (CBR) and Objective Response Rate (ORR) as well as
Progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST)
1.1 will be assessed. Study visits will be conducted according to the protocol schedule and
randomization group. Study visits will include physical examination, laboratory blood sample
collection, and assessment of vital signs, medical history and urinalysis. 12-lead
Electrocardiogram (ECG) will be performed at protocol specified visits.

Inclusion Criteria:

- Histologically or cytologically confirmed breast cancer that is either locally
recurrent or metastatic.

- Locally recurrent disease must not be amenable to surgical resection or radiation with
curative intent.

- Must have a documented deleterious Breast Cancer Gene BRCA1 or BRCA2 germline
mutation.

- If Human Epidermal Growth Factor Receptor (HER2) positive, subjects must have received
and progressed on at least one prior standard HER2 directed therapy or the subject
must be ineligible to receive anti-HER2 therapy.

- Measurable or non-measurable (but radiologically evaluable) disease by RECIST
(Response Evaluation Criteria in Solid Tumors) criteria 1.1.

- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.

- Subject must have adequate bone marrow, renal and hepatic function.

- Subject must not be pregnant or plan to conceive a child.

Exclusion Criteria:

- Received anticancer agent(s) or an investigational agent within 21 days prior to C1D1,
or radiotherapy within 28 days prior Cycle 1 Day 1

- More than 2 prior lines of cytotoxic chemotherapy

- Prior treatment of breast cancer with temozolomide, a platinum agent, or a Poly (ADP
ribose) Polymerase (PARP) inhibitor.

- Prior taxane therapy for metastatic breast cancer.

- A history of or evidence of brain metastases or leptomeningeal disease.

- A history of uncontrolled seizure disorder

- Pre-existing neuropathy from any cause in excess of Grade 1

- Known history of allergic reaction to cremophor/paclitaxel

- Clinical significant uncontrolled conditions â€" active infection, myocardial
infarction, stroke, or transient ischemic attack, psychiatric illness/social
situations that would limit compliance.

- Pregnant or breastfeeding