A Phase I/Ib Study of MEK162, a MEK Inhibitor, in Combination With Carboplatin and Pemetrexed in Patients With Non-squamous Carcinoma of the Lung

Inclusion Criteria: * Subjects eligible for enrolment on the study must meet all of the following criteria: * Patients with histologically confirmed non-squamous EGFR wild-type, ALK-rearrangement negative carcinoma of lung. Patients with neuroendocrine carcinoma, mixed small and non-small cell carcinoma or squamous carcinoma are not eligible. * Tissue available for KRAS mutation status analysis. * Patients must have metastatic disease (Incurable stage IIIB/stage IV). * Patients must have clinically and/or radiographically documented measurable disease. At least one site of disease must be unidimensionally measurable by RECIST v1.1 as follows (Eisenhauer et al.): CT-scan, physical exam ≥10 mm Chest X-ray ≥20 mm Lymph node short axis ≥15 mm * All radiology studies must be performed within 28 days prior to registration (35 days if negative). * Lesions in previously irradiated areas should not be selected unless there is clear evidence of progression in such lesions. * Patients may not have received any prior systemic treatment for metastatic NSCLC. Patients who have received adjuvant treatment or chemoradiation for stage III disease should have completed this ≥12 months prior to study enrollment. * Patients with stable CNS metastases are permitted if stability of disease is documented with imaging ≥28 days after treatment completion, are and off corticosteroids by day 1 of study treatment. * Patients may have had prior malignancy if definitively treated and/or, in the opinion of the investigator, the only active malignancy is NSCLC. Patients with mixed small cell lung cancer histology are excluded. Patients who have received radiotherapy to \>30% bone marrow are excluded. Consult PI if unsure whether second malignancies meet requirements specified above. * In patients treated for other malignancy, all prior treatment-related toxicities must be CTCAE v4.0 ≤ Grade 1 (except alopecia) at the time of enrollment. * Able to swallow and retain oral medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. * Patients receiving medications or substances that are inhibitors or inducers of CYP1A2, CYP2A19, CYP2B6, CYP3A4 and/or UGT1A1 and UGT1A9 are eligible but these drugs must be used with caution (Appendix C). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; * Patients must be aged ≥18 years. * Eastern Cooperative Oncology Group (ECOG) performance status ≤1 * Adequate organ and laboratory parameters, defined below. * Laboratory Requirements - within 7 days prior to enrollment: Haematology: absolute granulocytes ≥1.5 × 109/L platelets ≥100 × 109/L Biochemistry: bilirubin ≤1.25 × institutional upper limit of normal AST(SGOT) ≤2.5 × institutional upper limit of normal /ALT(SGPT) or ≤5 × institutional upper limit of normal in the presence of liver metastases creatinine clearance ≥45 mL/min/1.73 m2 -Patients must be able to provide Informed Consent based on the details below: * absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial * before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. Exclusion Criteria: * History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR): * History of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes). Patients with prior deep venous thrombosis or pulmonary embolism are permitted. * Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for RVO or CSR such as: * Evidence of new optic disc cupping * Evidence of new visual field defects on automated perimetry * Intraocular pressure \>21mmHg as measured by tonography * Any serious and/or unstable pre-existing medical (aside from malignancy exception), psychiatric disorder, or other conditions that could interfere with subjects' safety, obtaining informed consent or compliance to the study procedures, in the opinion of the PI. * History of interstitial lung disease or pneumonitis. * Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal metabolic or cardiac disease). * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events (e.g. congenital long QT syndrome, family history of long QT syndrome, hypokalemia) or baseline QTcB interval ≥480 msec. * History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months or cardiac metastases. * History or evidence of current clinically significant uncontrolled arrhythmias. * History or evidence of current ≥Class II congestive heart failure as defined by New York Heart Association (NYHA). * Known positivity for Hepatitis B surface antigen or Hepatitis C antibody. * Known Human Immunodeficiency Virus (HIV) infection. * Treatment refractory hypertension defined as a blood pressure systolic \>140 mmHg and/or diastolic \>90 mmHg which cannot be controlled by anti-hypertensive therapy. * Subjects with intra-cardiac defibrillators or permanent pacemakers. * Pregnant or nursing (lactating) women are excluded. * Female patient of child bearing potential must have a negative serum or urine pregnancy test. * Women of child-bearing potential must agree to use of appropriate contraceptive methods throughout the study and for 120 days after, These methods include * Total abstinence or 2 barrier methods or a barrier method plus hormonal method from visit 1 to 120 days after the last dose of treatment. * Men must agree to use an appropriate method of contraception starting with first dose of study drug through 120 days after the last dose of treatment (see above). * Whilst not excluded, patients with significant impaired hearing must be made aware of potential ototoxicity and may choose not to be included. If included, baseline audiograms are recommended and should be followed by repeat audiograms prior to cycle 2.