Talazoparib For Neoadjuvant Treatment Of Germline Brca1/2 Mutation Patients With Early Triple-negative Breast Cancer

TALAZOPARIB (PARP INHIBITOR) FOR NEOADJUVANT TREATMENT OF GERMLINE BRCA1/2 MUTATION PATIENTS
WITH EARLY TRIPLE NEGATIVE BREAST CANCER. THIS IS A MONOTHERAPY TREATMENT FOR 24 WKS FOLLOWED
BY SURGERY TO EVALUATE PATHOLOGICAL COMPLETE RESPONSE.

Inclusion Criteria:

- Germline BRCA 1/2 Mutation Positive

- Women and men at least 18 years of age or older.

- Histologically confirmed invasive triple negative Breast Cancer

- Tumor greater than or equal toT1

- No evidence of distant metastasis

- Adequate bone marrow, hepatic, and renal function

- ECOG performance status 0 or 1

Exclusion Criteria:

- Any other previous antitumor therapies for the current cancer event. Treatment for
ductal carcinoma in situ (DCIS) is allowed; ie, surgery, hormonal therapy and
radiation.

- Evidence of distant metastasis apparent prior to randomization

- Patients with inflammatory breast carcinoma

- Malignancy within the last 3 years, except:: Adequately treated non melanoma skin
cancer; Curatively treated in situ cancer of the cervix; Stage 1, Grade 1 endometrial
carcinoma; or Adequately treated contralateral breast carcinoma which has been disease
free for a year; Other solid tumors including lymphomas (without bone marrow
involvement) curatively treated with no evidence of disease for 5 years.

- Previous or concomitant systemic anti cancer therapies used for the treatment of
cancer in the last 3 years.

- Prior treatment with a PARP inhibitor in any disease setting

- Concomitant use of Strong P gp inhibitors or inducers or BCRP inhibitors

- Patients who are unwilling or unable to use 2 highly effective methods of
contraception as outlined in this protocol

- Major surgery within 14 days prior to study entry

- Known history of cardiac disease, for example : Myocardial infarction or symptomatic
cardiac ischemia within 24 weeks before screening; Congestive heart failure New York
Heart Association Class III or IV; History of clinically significant ventricular
arrhythmias within one year prior to randomization; History of Mobitz II second degree
or third degree heart block, uncontrolled hypertension.

- Active clinically significant infection

- Clinically significant bleeding diathesis or coagulopathy

- Non healing wound, ulcer or bone fracture

- Known hypersensitivity to any of the components of talazoparib

- Patients with myelodysplastic syndrome/acute myeloid leukemia

- Patients with uncontrolled seizures.

- Any evidence of other disease or any concomitant medical or psychiatric problems which
in the opinion of the Investigator would prevent completion of treatment