Binimetinib in Addition to Standard Chemotherapy in KRAS Mutated NSCLC.

Inclusion Criteria: * Written informed consent according to the Swiss HRA and ICH-GCP regulation before registration and prior to any trial-specific procedure. * Histologically or cytologically confirmed diagnosis of NSCLC, predominantly non-squamous subtype (adenocarcinoma, large cell carcinoma, NOS). * Locally advanced or metastatic stage III-IV disease according to the 7th TNM classification, ineligible for curative treatment. * Presence of KRAS exon 2 or 3 (codon 12, 13 or 61) mutations by local testing (concomitant EGFR and ALK mutations are excluded). * CT scan showing measurable disease, which is defined as at least one lesion that can be measured in at least one dimension (non-nodal lesions ≥10 mm in longest diameter, lymph nodes ≥15 mm in short axis) according to RECIST 1.1. * Eligible for cisplatin-based chemotherapy and able to take oral medications. * WHO performance status 0-1. * Age from 18 to 75 years. * Adequate hematological values: hemoglobin ≥ 90 g/L, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L. * Adequate hepatic function: total bilirubin ≤ 1.5 x ULN and \< 34.2 μmol/L; ALT and alkaline phosphatase ≤ 2.5 x ULN. * Adequate renal function: calculated creatinine clearance ≥ 60 mL/min, according to the formula of Cockcroft-Gault. * Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥ 50% as determined by echocardiogram; QTcF interval must be ≤ 480 ms. * Women with child-bearing potential are using effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and 6 months thereafter. A negative serum pregnancy test before inclusion into the trial is required for all women with child-bearing potential. * Men agree not to father a child during trial treatment and 6 months thereafter. Exclusion Criteria: * NSCLC with any additional small cell carcinoma (SCLC) component by local diagnostic pathology report. * Meningeosis carcinomatosa, symptomatic or untreated central nervous system (CNS) metastases. Patients with treated, controlled CNS metastases can be enrolled 2 weeks after the end of radiotherapy if asymptomatic (no residual neurologic deficits) and no longer on corticosteroids. * Previous or concurrent malignancy with the following exceptions: * adequately treated basal cell or squamous cell carcinoma of the skin (adequate wound healing is required prior registration), * in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 5 years prior registration, * superficial bladder cancer, prostate intraepithelial neoplasm, other noninvasive or indolent malignancy, or other solid tumor treated curatively and without evidence of recurrence for at least 5 years prior registration. * Leptomeningeal disease. * Concurrent radiotherapy (patients with prior radiotherapy other than for brain metastases ≥ 7 days prior to registration can be enrolled). * Previous systemic therapy for advanced NSCLC; previous adjuvant or neoadjuvant chemotherapy allowed if last dose was administered at least 6 months ago. * Major surgery within 3 weeks before registration. * Concurrent treatment with any other experimental drug or other anticancer therapy. * Impaired cardiovascular function or clinically severe or uncontrolled cardiovascular diseases, including any of the following: * congestive heart failure NYHA III or IV, * history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) \< 6 months prior to registration, * symptomatic chronic heart failure (G2 or higher), history or current evidence of clinically significant cardiac arrhythmia requiring medication and/or conduction abnormality \< 6 months prior to registration except atrial fibrillation and paroxysmal supraventricular tachycardia. * Uncontrolled arterial hypertension defined as persistent elevation of systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite medical treatment. * History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyper-viscosity or hypercoagulability syndromes); history of retinal degenerative disease. * History of Gilbert's syndrome. * Neuromuscular disorders that are associated with elevated creatine phosphokinase (CPK; e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy). * Neuropathy (\> G1) or hearing impairment/ tinnitus (\> G1). * Impairment of gastrointestinal function or gastrointestinal disease (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection). * History of thromboembolic or cerebrovascular events within 6 months prior to registration, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli. * Known history of acute or chronic pancreatitis. * History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) within 12 months prior to registration. * Known positive serology for HIV (human immunodeficiency virus), active hepatitis B, and/or active hepatitis C infection. * Active infection within 14 days prior to registration. * Planning on embarking on a new strenuous exercise regimen after first dose of binimetinib (NB: muscular activities, such as strenuous exercise, that can result in significant increases in plasma CPK levels should be avoided while on binimetinib treatment). * Known lactose intolerance. * Known hypersensitivity to the trial drugs or hypersensitivity to any other component of the trial treatment, including premedication. * Any concomitant drugs contraindicated for use with pemetrexed and cisplatin according to the Swissmedic-approved current product information or with binimetinib according to the latest version of the Investigator's Brochure. * Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.