Inclusion Criteria:
- Signed informed consent
- Tumor accessible to biopsy and willingness to undergo tumor biopsy
- Age >= 18 years
- Recurrent, histologically documented NSCLC, i.e., squamous cell, adeno-, or large cell anaplastic carcinoma. A cytologic diagnosis is acceptable (i.e. fine-needle aspiration or pleural fluid cytology).
- Measurable disease with at least one lesion that can be accurately measured in at least one dimension (bilateral dimensions should be recorded). Each lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain X-ray, CT, and MRI, or >= 10 mm when measured by spiral CT.
- Progression of disease during, or after completion of, at least one prior chemotherapy regimen, which should have contained either a platinum, a taxane or a vinca alkaloid (e.g. vinorelbine). There is no upper limit on the number of prior chemotherapy regimens each subject may have received.
- Recovery from reversible acute effects of prior chemotherapy regimens or radiotherapy to NCI-CTC Grade <= 1 (excluding alopecia)
- ECOG performance status of 0 or 1
- Use of an effective means of contraception for men, or for women of childbearing potential
- Absolute neutrophil count >= 1500/mL, platelet count of >= 75,000/mL and hemoglobin >= 9 g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbepoetin [Aranesp] is permitted)
- Serum bilirubin <= 1.5 x the upper limit of normal (ULN) and alkaline phosphatase, AST, and ALT <= 2.5 x ULN (ALT, AST, and alkaline phosphatase <= 5 x ULN for subjects with liver metastases)
- Serum creatinine <= 1.5 x ULN
- Internalized normalized ratio (INR) < 1.5 and activated partial thromboplastin time (aPTT) < 1.5 ULN (except for subjects receiving warfarin)
Exclusion Criteria:
- Prior treatment with any HER pathway inhibitors (e.g., Herceptin [Trastuzumab], Iressa [gefitinib], Tarceva [erlotinib hydrochloride], C225, CI1033, TAK165
- Treatment with other experimental anti-cancer agents within 4 weeks prior to Day 1
- Histologically documented bronchioalveolar carcinoma
- History or clinical or radiographic evidence of central nervous system or brain metastases
- Ejection fraction, determined by ECHO, <50%
- Uncontrolled hypercalcemia (> 11.5 mg/dL)
- Prior exposure of > 360 mg/m2 doxorubicin or liposomal doxorubicin, > 120 mg/m2 mitoxantrone, or > 90 mg/m2 idarubicin
- Ongoing corticosteroid treatment, except for subjects who are on stable doses of < 20 mg of prednisone daily (or equivalent), or for subjects who are taking corticosteroids for non-malignant conditions
- History of other malignancies within 5 years of Day 1 except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, or basal or squamous cell skin cancer
- History of serious systemic disease, uncontrolled hypertension (diastolic blood pressure > 100 mmHg on two consecutive occasions), unstable angina, congestive heart failure, or myocardial infarction within 6 months prior to Day 1, or unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, or controlled hypertension are eligible)
- Ongoing liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- Active infection requiring IV antibiotics
- Known human immunodeficiency virus infection
- Pregnancy or lactation
- Major surgery or significant traumatic injury within 3 weeks prior to Day 1, with the exception of tumor biopsy for the purposes of the study
- Inability to comply with study and follow-up procedures
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
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