Pembrolizumab and Trametinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer and KRAS Gene Mutations

Inclusion Criteria

• Stage IV or metastatic/recurrent non-small cell lung cancer; for expansion cohorts, patient's tumor must also harbor a KRAS mutation detected in a CLIA certified laboratory
• Have histologically or cytologically confirmed non-small cell lung cancer
• Have stage IV, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) with progressive disease after platinum containing chemotherapy (EGFR mutant, ALK, or ROS-1 rearranged NSCLC must have progressed on prior approved tyrosine kinase inhibitor [TKI]'s)
• For phase I dose expansion cohorts the patient's tumor must harbor a KRAS mutation detected by a CLIA certified laboratory
• Be willing and able to provide written informed consent/assent for the trial
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; in the opinion of the investigator, the patient must have tumor accessible by CT or ultrasound guided core biopsy; subjects for whom newly-obtained samples cannot be provided may submit an archived specimen provided it was obtained after last systemic treatment, within 6 months of signing consent and that tissue is available for either 2 cell blocks or 20 uncut slides (core or excisional biopsy required, fine needle aspirate is not acceptable)
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• Able to swallow and retain orally administered 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
• Absolute neutrophil count >= 1.5 x 10^9/L
• Hemoglobin >= 9 g/dL
• Platelets >= 100 x 10^9/L
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) = = 2.5 g/dL
• Total bilirubin = = 50 mL/min
• Left ventricular ejection fraction (LVEF) >= lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition (MUGA)
• Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication; note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy; note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible

Exclusion Criteria

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 3 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment; inhaled or topical steroids are allowed
• Has a known history of active tuberculosis (TB [Bacillus Tuberculosis])
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study day 1 or who has not recovered (i.e., = = 470 msec on screening exam
• History or evidence of current clinically significant uncontrolled arrhythmias
• History of acute coronary syndromes (including myocardial infarction and unstable