A Phase 1/2, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Subjects With Solid Tumors And ErbB-2 Positive Metastatic Or Locally Advanced Breast Cancer

Inclusion Criteria:

- Part 1: confirmed pathologic diagnosis of a solid tumor not curable with available
therapies for which neratinib plus capecitabine is a reasonable treatment option.

- Part 2: confirmed histologically and/or cytologically confirmed diagnosis of breast
cancer, metastatic or locally advanced.

- Part 2: erbB-2 gene amplified tumor (FISH or CISH) or erbB-2 overexpression (IHC 3+,
or IHC2+ with FISH or CISH confirmation), based on local testing, or based on
centralized FISH testing prior to day 1.

- Part 2: disease progression on or following at least 1 prior trastuzumab containing
treatment regimen (at least 6 weeks) for metastatic or locally advanced disease.
(Prior adjuvant trastuzumab is allowed but not required). A 2 week period is required
between the last dose of trastuzumab treatment and first dose of the test article.

- Prior treatment with a taxane in the neoadjuvant, adjuvant, locally advanced, and/or
metastatic disease treatment setting.

- Parts 1+2: At least 1 measurable lesion as defined by RECIST criteria.

- Parts 1+2: LVEF within institutional range of normal as measured by multi-gated
acquisition (MUGA) or echocardiogram (ECHO).

Exclusion Criteria:

- Part 2: prior treatment with capecitabine, lapatinib (20 subjects with prior
lapatinib exposure will be enrolled) or any erbB-2 targeted agents except
trastuzumab. Treatment with erbB-2 targeted therapy must exceed 2 weeks (14 days) in
order to be exclusionary.

- Part 2: prior treatment with anthracyclines with a cumulative dose of doxorubicin of
greater than 400 mg/m2, epirubicin dose of greater than 800 mg/m2, or the equivalent
dose for other anthracyclines.

- Parts 1+2: Subjects with bone as the only site of disease.

- Parts 1+2: Active uncontrolled or symptomatic central nervous system (CNS)
metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive
growth. Subjects with a history of CNS metastases or cord compression are allowable
if they have been considered definitively treated and are off anticonvulsants and
steroids for at least 4 weeks before the first dose of test article.

- Parts 1+2: Any other cancer within 5 years prior to screening with the exception of
adequately treated cervical carcinoma in situ, or adequately treated basal or
squamous cell carcinoma of the skin.