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