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

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., =\< grade 1 or at baseline) from adverse events due to agents administered more than 3 weeks earlier

Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent; note: subjects with =\< grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study; note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy

Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer

Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability

Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

Has known history of, or any evidence of active, non-infectious pneumonitis; history of radiation pneumonitis is allowed provided that it is not active and no corticosteroids were required for pneumonitis management

Evidence of interstitial lung disease

Has an active infection requiring systemic therapy

Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, or excipients or to dimethyl sulfoxide (DMSO)

History of retinal vein occlusion (RVO)

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment

Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent for dose expansion; (patients in dose escalation may have received an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent)

Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)

Has known active Hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive) or Hepatitis C (e.g., hepatitis C virus (HCV) ribonucleic acid (RNA) \[qualitative\] is detected)

LVEF \< LLN on screening exam

A QT interval corrected for heart rate using the Fridericia's formula (QTcF) \>= 470 msec on screening exam

History or evidence of current clinically significant uncontrolled arrhythmias

History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrollment

History or evidence of current \>= class II congestive heart failure as defined by New York Heart Association (NYHA)

Treatment refractory hypertension defined as a blood pressure of systolic \> 140 mmHg and/or diastolic \> 90 mm Hg which cannot be controlled by anti-hypertensive therapy

Patients with intra-cardiac defibrillators

Has received a live vaccine within 30 days of planned start of study therapy; note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

What this study is about