Pembrolizumab and Stereotactic Body Radiation Therapy or Non-Stereotactic Wide-Field Radiation Therapy in Treating Patients With Non-small Cell Lung Cancer

Inclusion Criteria

• Pathologically confirmed non-small lung cancer; for patients in group 5, any solid tumor histology to be included
• Stage IV metastatic disease (only during the phase II)
• At least one thoracic or liver lesion amenable to radiation, for group 5 we need one area that can safely receive SBRT or WFRT, not restricted to lung or liver sites
• At least one additional non-contiguous lesion to the irradiated lesion amenable to radiographic evaluation
• Be willing and able to provide written informed consent/assent for the trial
• Have measurable disease based on immune related response criteria (irRC) criteria
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) >= 1, 500 /mcL (performed within 28 days prior to study registration up to the first dose of study drug)
• Platelets >= 100, 000 /mcL (performed within 28 days prior to study registration up to the first dose of study drug)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (performed within 28 days prior to study registration up to the first dose of study drug)
• Serum creatinine = = 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (creatinine clearance should be calculated per institutional standard) (performed within 28 days prior to study registration up to the first dose of study drug)
• Serum total bilirubin = 1.5 ULN (performed within 28 days prior to study registration up to the first dose of study drug)
• Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) = 1 year
• Male subjects should 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
• We will allow XRT prior to study entry to other sites, with no washout period, allowed prior to study entry as long as at least one measurable sites of disease is kept unirradiated

Exclusion Criteria

• Is currently participating in or has participated in a study of an investigational agent (except glutamine) or using an investigational device within 4 weeks of the first dose of treatment or 5 half lives, whichever is shorter
• 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; unless the steroid therapy is for physiological replacement
• Has a diagnosis of active scleroderma, lupus, or other autoimmune disease which by the opinion of the treating radiation oncologist precludes safe radiation therapy
• Has had prior radiation therapy to all available thoracic and liver lesions such that additional radiation therapy is unsafe by the opinion of the treating radiation oncologist
• Has had a prior monoclonal antibody within 4 weeks or 5 half-lives, which ever is shorter, 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 4 weeks earlier
• Has had prior chemotherapy or targeted small molecule 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 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, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastase