Pemetrexed and LBH589 in Patients With Advanced Non-Small Cell Lung Cancer

Inclusion Criteria: 1. Phase I only: any number of prior regimens is allowed and all thoracic malignancies, except squamous cell carcinoma of the lung. 2. Phase II only: Patients with recurrent or progressive advanced stage non-squamous cell NSCLC (no small cell lung cancer/SCLC component) who have received 1 prior chemotherapy regimen for advanced NSCLC. Chemotherapy as part of initially potentially curative therapy that was completed \<1 year counts as 1 prior regimen. Prior erlotinib or one other biologic regimen is also allowed. 3. Measurable disease (RECIST) (for phase II part only) 4. Patients may not have received prior pemetrexed or histone deacetylase inhibitor (HDACi) therapy, including valproic acid, for the treatment of any medical condition. 5. ECOG (Eastern Cooperative Oncology Group) Performance Status of ≤ 2 6. Aged ≥ 18 years old and ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed 7. Patients must meet the following laboratory criteria: * Hematology: * Absolute neutrophil count (ANC) ≥ 1500/mm³ * Platelets ≥ 100,000/mm³ * Hemoglobin ≥ 9 g/dL * Biochemistry: * Total Bilirubin within normal institutional limits. * Aspartate aminotransferase/glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x upper limit of normal (ULN) * Creatinine clearance 45 ml/min or higher calculated using the Cockcroft-Gault formula * Total serum calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) * Serum potassium ≥ WNL * Serum sodium ≥ WNL * Serum albumin ≥ WNL * Patients with any elevated Alkaline Phosphatase due to bone metastasis can be enrolled 8. Baseline multiple uptake gated acquisition scan (MUGA) or ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal. 9. Thytoid stimulating hormone (TSH) and free T4 within normal limits (patients may be on thyroid hormone replacement) 10. Blood pressure of \<140/90. 11. Patients must have fully recovered from the effects of any prior surgery, chemotherapy or radiation therapy. A minimum time period of 3 weeks should elapse between the completion of extensive radiation therapy for recurrent/metastatic disease and enrollment in the study. A minimum of 4 weeks should elapse between the completion of chemotherapy or any experimental therapy and enrollment in the study. At least 2 weeks should have elapsed from prior erlotinib or other biologic therapy. 12. If patient has history of brain metastases, brain lesions should have been treated with surgery and/or radiation and be stable on repeat imaging. 13. No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a 3- year disease-free interval. 14. Patients should temporary stop certain Nonsteroidal Anti-inflammatory Drug (NSAIDS) starting 5 days prior to protocol therapy, as described in 6.5.1. 15. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study treatment and must be willing to use two methods of contraception one of them being a barrier method or abstain from sexual activity during the study and for 3 months after last study drug administration. Sexually active males and their female partners must agree to use two methods of accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study. 16. All patients must have given signed, informed consent prior to registration on study. Exclusion Criteria: 1. Prior HDAC, deacetylase (DAC), HSP90 inhibitors or valproic acid for the treatment of cancer 2. Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment 3. Impaired cardiac function including any one of the following: * Screening ECG with a QTc \> 450 msec confirmed by central laboratory prior to enrollment to the study * Patients with congenital long QT syndrome * History of sustained ventricular tachycardia * Any history of ventricular fibrillation or torsades de pointes * Bradycardia defined as heart rate \< 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible. * Patients with a myocardial infarction or unstable angina within 6 months of study entry * Congestive heart failure (NY Heart Association class III or IV) * Right bundle branch block and left anterior hemiblock (bifascicular block) 4. Uncontrolled hypertension. Patients with history of hypertension must be well-controlled (≤150/100) on a stable regimen of anti-hypertensive therapy. 5. Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix 1.-1) 6. Concomitant use of Cytochrome (CYP3A4) inhibitors (See Appendix 1-2) is not allowed. The use of cytochrome (CYP2D6) substrates (Appendix 1, table 0-3) should be done with caution. If drugs that are CYP2D6 substrates arte to be continued, patients should be carefully monitored and may require dose titration or dose reduction of the CYP2D6 substrate. 7. Patients with unresolved diarrhea \> CTCAE (NCI common terminology criteria for adverse events ) grade 1 8. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589 9. Other concurrent severe and/or uncontrolled medical conditions 10. Patients who have received chemotherapy, any investigational drug or undergone major surgery \< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy. 11. Concomitant use of any anti-cancer therapy or radiation therapy. 12. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589. 13. Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom 14. Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required 15. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent 16. Patients with squamous cell carcinomas will be excluded