Pembrolizumab After Radiation Therapy in Treating Patients With Pleural Malignant Mesothelioma

Inclusion Criteria

• Patients must have a histologic diagnosis of malignant pleural mesothelioma, with histologic diagnosis from the pleura or relevant lymph node stations, including mediastinal, hilar, or supraclavicular lymph nodes
• Be willing and able to provide written informed consent/assent for the trial
• Have measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; however, note that patients in Cohort 1 that have undergone an R0 resection will be eligible for the trial
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) >=1, 500 /mcL (within 10-15 days of treatment initiation)
• Platelets >= 100, 000 /mcL (within 10-15 days of treatment initiation)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (within 10-15 days of treatment initiation)
• Serum creatinine = = 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (within 10-15 days of treatment initiation)
• Serum total bilirubin = 1.5 ULN (within 10-15 days of treatment initiation)
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) = = 2.5 mg/dL (within 10-15 days of treatment initiation)
• International normalized ratio (INR) or prothrombin time (PT) = 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
• COHORT 1 (PATIENTS RECEIVING HEMITHORACIC RADIATION THERAPY)
• Patients must not have evidence of metastatic disease per positron emission tomography (PET)/ computed tomography (CT) scan; mediastinal lymph node involvement is acceptable
• Patients will have received at least 2 cycles of induction chemotherapy with pemetrexed/cisplatin or pemetrexed/carboplatin
• Forced expiratory volume in 1 second (FEV1) >= 30% of predicted postoperative (ppoFEV1, as if patient underwent a pneumonectomy)
• Diffusing capacity of the lungs for carbon monoxide (DLCO) > 35% predicted
• Patients must be assessed to be a suitable candidate for hemithoracic radiation therapy per the treating radiation oncologist; if the patient undergoes pleurectomy/decortication, they must initiate hemithoracic radiation therapy within 4 months of the surgery date; patients that do not meet the dose constraints outlined below will be removed from the study prior to radiation therapy
• COHORT 2 INCLUSION CRITERIA
• Patients must be assessed to be a suitable candidate for radiation therapy by the treating radiation oncologist; patients that do not meet the dose constraints outlined below will be removed from the study prior to radiation therapy
• Any prior number of prior therapies, including prior immunotherapy, is allowed
• Patient must have prior treatment with a platinum plus pemetrexed regimen

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; note that patients should not receive steroids during pembrolizumab administration
• 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 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, or radiation therapy within 2 weeks prior to study day 1 and who have not recovered adequately from this treatment (=< grade 2 toxicity at the time of enrollment)
• Has a known additi