Inclusion Criteria

Criteria for Inclusion:

1. ≥ 18 year old males or females

2. Documented measurable or evaluable solid tumor malignancy that is relapsed,
refractory, locally advanced, or metastatic

3. Patients entered to MTD Cohort B must have:

- Histologically or cytologically confirmed NSCLC

- No prior therapy with erlotinib, gefitinib, or any other EGFR-kinase inhibitor

- Previously documented exon 19 deletion and/or exon 21 L858R mutations

- Measurable disease according to RECIST

4. Disease that is currently refractory to, or not amenable to, standard therapy

5. Disease that is currently not amenable to surgical intervention, due to either
medical contraindications or nonresectability of the tumor

6. Karnofsky performance status ≥ 70%, life expectancy ≥ 3 months

7. No childbearing potential or use of effective contraception by all fertile male and
female patients, during the study and for 3 months after the last dose of study drug

8. Ability to give written informed consent

Criteria for Exclusion:

1. Pregnant or lactating women

2. Primary CNS malignancies; active CNS metastases

3. Hematologic malignancies (includes: leukemia, any form; lymphoma; and multiple
myeloma)

4. Active second malignancy or history of another malignancy within 2 years with the
exception of:

- Treated, non-melanoma skin cancers

- Treated CIS of the breast or cervix

- Controlled, superficial bladder carcinoma

- T1a or b prostate carcinoma involving < 5% of resected tissue and PSA within
normal limits (WNL)

5. Any of the following hematologic abnormalities:

- Hemoglobin ≤ 9.0 g/dL

- ANC < 1,500 per mm3

- Platelet count < 100,000 per mm3

6. Any of the following serum chemistry abnormalities:

- Total bilirubin > 1.5 × the ULN

- AST or ALT ≥ 3 × the ULN (≥ 5 × if due to hepatic involvement by tumor)

- Serum albumin < 2.5 g/dL

- Creatinine ≥ 1.5 × ULN (or calculated CLCR < 50 mL/min/1.73 m2)

7. Significant cardiovascular disease, including:

- CHF requiring therapy

- Ventricular arrhythmia requiring therapy

- Any conduction disturbance (including patients with QTc interval prolongation >
0.47 sec, history of a severe arrhythmia, or history of a familial arrhythmia
[eg, WPW])

- Angina pectoris requiring therapy

- LVEF < 50% by MUGA or Echocardiogram

- Uncontrolled HTN

- MI within 6 months of study entry

- NYHA > Class I

8. Significant gastrointestinal abnormalities, including:

- Requirement for IV alimentation

- Prior surgical procedures affecting absorption

- Active peptic ulcer disease

- ≥Grade 2 diarrhea due to any etiology

9. Known history of significant ophthalmologic abnormalities, including:

- Severe dry-eye syndrome

- Keratoconjunctivitis sicca

- Sjogren's syndrome

- Severe exposure keratopathy

- Disorders increasing risk for epithelium-related complications

10. Serious/active infection; infection requiring parenteral antibiotics

11. Inadequate recovery from prior antineoplastic therapy

12. Inadequate recovery from any prior surgical procedure; major surgical procedure
within 2 weeks

13. Life-threatening illness or organ system dysfunction compromising safety evaluation

14. Psychiatric disorder, altered mental status precluding informed consent or necessary
testing

15. Inability to comply with protocol requirements