Study of Poziotinib in Patients With HER2-Positive Metastatic Breast Cancer

This is a phase 2, open-label, multicenter study to establish the dose regimen and evaluate
the preliminary efficacy and the safety/tolerability of poziotinib in patients with
HER2-positive metastatic breast cancer who have received at least 2 prior HER2-directed
treatment regimens.

Each treatment cycle will be 21 days in duration. During each 21-day cycle, patients who are
eligible for participation will receive poziotinib orally once daily.

All treated patients will be followed up until disease progression, death, intolerable
adverse events or up to a maximum of 24 months whichever comes earlier.

Inclusion Criteria:

1. Histopathologically confirmed primary breast cancer with metastatic lesions.

2. Confirmed HER2 overexpression or gene-amplified tumor

3. At least two prior HER2-directed therapy regimens for breast cancer, including
trastuzumab and trastuzumab emtansine (TDM-1, KADCYLA®)

4. Patient is at least 18, and ≤90 years of age.

5. Patient has adequate hematologic, hepatic, and renal functions

6. At least one measurable lesion

Exclusion Criteria:

1. Previous treatment with poziotinib prior to study participation.

2. Brain metastases that are symptomatic or require therapy to control symptoms, as well
as any history of radiation, surgery, or other therapy, including steroids, to control
symptoms from brain metastases within 15 days of enrollment.

3. Anticancer chemotherapy, biologics, immunotherapy, cure-intent radiotherapy, or
investigational treatment within 15 days, except for hormone therapy, palliative
therapy, or supportive therapy.

4. History of congestive heart failure (CHF) Class III/IV according to the New York Heart
Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring
treatment.

5. Patient has a cardiac ejection fraction <50%

6. Patient has a history of other malignancies within the last 5 years

7. Unable to take drugs orally

8. Patient is pregnant or breast-feeding.