Inclusion Criteria:

- Pathologic diagnosis of NSCLC and current stage IIIB (with pleural effusion) or IV,
not curable with conventional therapy. For Arm C, less than or equal to 20 pack-years
smoking history and current non smoker. A pack year = number of packs of cigarettes
smoked per day x years smoked.

- Progression following at least 12 weeks of treatment with Tarceva or Iressa. (Arms A
and B only)

- ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2 (not
declining within past 2 weeks).

- Tumor sample available and adequate for analysis.

- At least one measurable target lesion.

- Adequate cardiac, kidney, and liver function

- Adequate blood counts

Exclusion Criteria:

- More than 3 prior cytotoxic chemotherapy treatments for relapsed or metastatic
disease.

- Significant cardiac disease or dysfunction.

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

- Active central nervous system metastases, as indicated by clinical symptoms and/or
progressive growth.

- Use of Tarceva or Iressa within 14 days of treatment day 1 (Arms A and B only).

- Major surgery, chemotherapy, radiotherapy, investigational drugs, or other cancer
therapy within 3 weeks of treatment day 1.

- Significant chronic or recent acute gastrointestinal disorder with diarrhea as a
major symptom.

- Inability or unwillingness to swallow HKI-272 capsules.

- Pregnant or breastfeeding women.