BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer

Inclusion Criteria

• The subject has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or fine-needle aspiration.
• The subject has a diagnosis of either advanced, incurable stage IIIB or stage IV NSCLC, and failed at least one front-line metastatic NSCLC chemotherapy regimen, or EGFR TKI. (Subjects who have failed adjuvant or locally advanced therapy within 6 months are also eligible to participate in the study).
• The subject has measurable NSCLC (patients with active new disease growth in previously irradiated site are eligible).
• The subject's ECOG performance status is /= 1,500/mm3, platelet count >/= 100,000/mm3, WBC >/= 3,000/ mm3, and hemoglobin >/= 9 g/dL.
• The subject has adequate hepatic function as defined by a total bilirubin level /= 1.5 x ULN with known Gilbert's disease is allowed), and alkaline phosphatase, AST and ALT 50ml/min, either by Cockcroft-Gault formula or 24-hour urine collection analysis
• If subject has brain metastasis, they must have been stable (treated and/or asymptomatic) and off steroids for at least 2 weeks.
• The subject is >/=18 years of age.
• The subject has signed informed consent.
• The subject is eligible if disease free from a previously treated malignancy, other than a previous NSCLC, for greater than two years. Subject with a history of prior basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix are allowed.
• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Childbearing potential will be defined as women who have had menses within the past 12 months, who have not had tubal ligation, hysterectomy or bilateral oophorectomy. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately.
• The subject, if a man, agrees to use effective contraception or abstinence while on study and for 90 days after last dose of study drug.
• Subject is able to swallow capsules and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis.

Exclusion Criteria

• The subject has received prior chemotherapy, surgery, or radiotherapy within 3 weeks of initiating study drug, or 4 weeks for bevacizumab or investigational drug or 72 hours for erlotinib or the subject has not recovered ( 140/90 despite optimal therapy, uncontrolled angina, ventricular arrhythmias, or congestive heart failure New York Heart Association Class II or above, baseline LVEF 100 bpm, unstable ischaemic heart disease (MI within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly).
• The subject has neuropathy >/= grade 2
• The subject is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding. In the event of inconclusive pregnancy test results, the investigator will have final determination of pregnancy status.
• Subjects will be excluded for other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, severe infection requiring active treatment, severe malnutrition, chronic severe liver or renal disease).
• Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
• Subjects with poorly controlled diabetes (HbA1c >8%) are excluded.
• Subjects whose tumor harbors the EML4-ALK fusion gene are excluded unless the patient has failed treatment with Anaplastic Lymphoma Kinase (ALK) inhibitor.
• Subjects are excluded if they have QTc prolongation >450 msec (Bazett's Formula) for males or >470 ms for females on screening or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart fail