A Phase 1/2 Trial of Trametinib and Erlotinib in Patients With EGFR-Mutant Lung Adenocarcinomas and Acquired Resistance to Erlotinib

Inclusion Criteria: * Pathologic evidence of advanced stage IV or recurrent lung adenocarcinoma reviewed at MSKCC * Somatic activating mutation in EGFR Radiographic progression during treatment with erlotinib. * Any number of prior chemotherapy regimens is permitted. * Measurable (RECIST 1.1) indicator lesion not previously irradiated * KPS \>/= 70% * Age \>18 years old * Must have undergone biopsy after development of acquired resistance to erlotinib with available archived tissue (equivalent of \> 10 unstained slides) * Left ventricular Ejection Fraction \>/= the lower limit of normal by ECHO or MUGA * Adequate organ function: * AST, ALT \</= 2.5 x ULN * Total bilirubin \</= 1.5 x ULN * Albumin\>/=2.6g/dL - Creatinine \< 1.5 x ULN OR calculated creatinine clearance \>/=50mL/min * Absolute neutrophil count (ANC) \>/= 1,200 cells/mm3 * Hemoglobin\>/=9.0 g/dL * Platelets \>/=100,000/mm3 Exclusion Criteria: * Patients with symptomatic brain metastasis requiring escalating doses of steroids * Patients with grade 2 or greater diarrhea prior to study initiation despite maximal medical management due to medications or a medical condition such as Crohn's disease or malabsorption * Pregnant or lactating women * Any type of systemic therapy (chemotherapy or experimental drugs) within 2 weeks of starting treatment on protocol except for a EGFR TKI * Patients who have received prior treatment with a MEK inhibitor * Any major surgery or extensive radiotherapy within 21 days of starting treatment on protocol. * A history of clinically significant interstitial lung disease or pneumonitis * Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study administration, New York Heart Association Class III or IV congestive heart failure, or symptomatic uncontrolled Arrythmias, prolonged corrected QT interval \>480msec, treatment refractory hypertension, presence of a cardiac defibrillator * History of central serous retinopathy or retinal vein occlusion