A Phase 1/2 Study of HKI-272 (Neratinib) in Combination With Paclitaxel (Taxol) in Subjects With Solid Tumors and Breast Cancer

Inclusion Criteria:

Inclusion criteria for both parts of clinical trial:

- Good performance status

- Normal ejection fraction

- Adequate cardiac, kidney, and liver function

- Adequate blood counts

- At least one measurable target lesion

- Negative pregnancy test for female subjects

Inclusion Criteria for Part 1 Only:

- Pathologically confirmed solid tumor not curable with available standard therapy

Inclusion Criteria for Part 2 Only:

- Pathologically confirmed breast cancer

- HER2 positive tumor

- Prior treatment with Herceptin

Exclusion Criteria:

Exclusion criteria for both parts of clinical trial:

- Major surgery, radiotherapy, chemotherapy or investigational agents within two weeks
of treatment day 1

- Subjects with bone or skin as the only site of disease

- Active central nervous system metastases

- Significant cardiac disease or dysfunction

- Significant gastrointestinal disorder

- Inability or unwillingness to swallow HKI-272 capsules

- Prior exposure to HKI-272 or other HER2 targeted agents, except trastuzumab (Part 2
only). Prior lapatinib is permitted in arm B of part 2.

- Treatment with a taxane within 3 months of treatment day 1

- Grade 2 or greater motor or sensory neuropathy

- Pregnant or breast feeding women

- Known hypersensitivity to paclitaxel or Cremophor EL

- Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2

- Any other cancer within 5 years with the exception of contralateral breast cancer,
adequately treated cervical carcinoma in situ, or adequately treated basal or squamous
cell carcinoma of the skin

Exclusion Criteria for Part 2 Only:

- More than 1 (arm A) or 3 (arm B) prior cytotoxic chemotherapy regimen for metastatic
disease