Pembrolizumab and Radiation Therapy in Treating Patients with Metastatic Non-small Cell Lung Cancer

Inclusion Criteria

• Histologically documented, metastatic NSCLC
• Patients with EGFR and ALK alterations should have been treated with at least 1 line of targeted tyrosine kinase inhibitor
• At least 2 distinct measurable metastatic sites, which are 1 cm or larger; patients can have radiation to multiple measurable disease sites as clinically indicated, however, there must be at least 1 measurable non-radiated target lesion for primary endpoint assessment of abscopal response
• Agreeable and clinically feasible pre-treatment biopsy if archival tissue is not available and an exception is not granted by the sponsor investigator
• 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 archival tissue of any age or tissue from a newly obtained core or excisional biopsy of a tumor lesion if an exception is not granted by the sponsor investigator
• Have a performance status of =< 1 Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 10 days of treatment initiation)
• Platelets >= 100,000/mcL (performed within 10 days of treatment initiation)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 10 days of treatment initiation)
• Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) =< 1.5 X upper limit of normal (ULN) OR >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (performed within 10 days of treatment initiation)
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 10 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (performed within 10 days of treatment initiation)
• Albumin >= 2.5 mg/dL (performed within 10 days of treatment initiation)
• Have one measurable lesion outside of the planned radiation field (defined as not receiving direct beam from any of the treatment portals)
• Female subject of childbearing potential should have a negative urine or serum pregnancy 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

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 4 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
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 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 4 weeks earlier
• Has had prior chemotherapy, targeted small molecule therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 2 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 * Exception: any adverse events (AEs) related to adequate organ function laboratory values that are within parameters listed above adequate organ function is met per Laboratory Values
• Patient who have previously received radiation overlapping with the current planned radiation treatment fields are ineligible; overlap is defined as any tissue falling within the direct path of both prior and current planned radiation fields
• 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 clinically stable for at least 4 weeks and, have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication; stable brain metastases by this definition should be established prior to the first dose of pembrolizumab
• Has had prior chemotherapy, within 2 weeks prior to study treatment; patients on targeted therapy (tyrosine kinase inhibitor) may go on the study after 5 days off therapy; patients can be screened but cannot start study treatment until after the above washout period
• Patients who have an 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• 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
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• 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