Dacomitinib + Pemetrexed for Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC)

Inclusion criteria: * Written informed consent * Histologically or cytologically confirmed stage IV non-squamous NSCLC * Patients who are candidates to receive pemetrexed monotherapy * If pemetrexed has been administered as first line therapy there must be a treatment free interval of at least one cycle (21 days) * Measurable disease by RECIST criteria version 1.1. * ≥18 years of age * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 * Adequate left ventricular ejection fraction (LVEF) ≥ 50% by either echocardiogram or multigated acquisition scan (MUGA) * Adequate organ function, including: 1. Adequate bone marrow reserve: absolute neutrophil count (ANC) should be ≥ 1500 cells/mm3, platelets should be ≥ 100.000 cells/mm3 2. Creatinine clearance ≥ 45 mL/min 3. Total bilirubin ≤ 1.5 x upper normal limit (ULN) 4. Aspartate Aminotransferase (AST) (SGOT) ≤ 3 x ULN (≤ 5.0 x ULN if hepatic metastases) 5. Alanine Aminotransferase (ALT) (SGPT) ≤ 3 x ULN (≤ 5.0 x ULN if hepatic metastases) * Female patients or their partners must be postmenopausal (defined as 12 months of amenorrhea following last menses), surgically sterile or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter (the definition of effective contraception will be based on the judgment of the investigator). Male patients or their partners must be surgically sterile or must agree to use a barrier method of contraception while receiving trial treatment and for at least 3 months thereafter. (In all cases the definition of effective contraception will be based on the judgment of the investigator). * Able to comply with required protocol procedures and able to receive oral medications Exclusion criteria: * Any evidence of mixed histology that includes elements of small cell or carcinoid lung cancer * Predominantly squamous cell histology * Patients with symptomatic brain metastases * Chemotherapy, radiotherapy, biological or investigational agents within two weeks of baseline disease assessments * Patients with uncontrolled or significant cardiovascular disease, including: 1. Myocardial infarction within 12 months 2. Uncontrolled angina within 6 months 3. Congestive heart failure within 6 months 4. Diagnosed or suspected congenital long QT syndrome 5. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) 6. Prolonged QTc interval on pre-entry electrocardiogram. QTc must be less than CTC Grade 2 (≤480 msec) using appropriate correction formula with manual read by investigator if required. The echocardiogram (ECG) may be repeated for evaluation of eligibility after management of correctable causes for observed QTc prolongation 7. Any history of second or third degree heart block (may be eligible if currently have a pacemaker) 8. Heart rate \<50/minute on baseline electrocardiogram 9. Uncontrolled hypertension * Prior malignancy: Patients will not be eligible if they have evidence of other malignancy (other than non-melanoma skin cancer or in situ cervical cancer, or localized and presumed cured prostate cancer with prostate specific antigen (PSA) \< ULN) within the last 3 years. * Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start. Known hypersensitivity to pemetrexed and/or dacomitinib * Patients with exposure to other investigational drug therapy * Previous therapy with an oral tyrosine kinase inhibitor (TKI)