Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma

Inclusion Criteria: * Patients must have histologically confirmed malignant pleural mesothelioma. Patients must be eligible to receive standard chemotherapy with pemetrexed and cisplatin and have no contraindications to standard chemotherapy. * Patients must have unresectable advanced and/or metastatic disease, incurable by standard therapies. * All patients must have a cellular tumour block from their primary or metastatic tumour available and consent to release the block/recently cut slides for correlative analyses (See Section 11.0) and the centre/pathologist must have agreed to the submission of the specimen(s). * Presence of radiologically documented disease. At least one site of disease must be unidimensionally measurable as follows: * CT scan (with slice thickness of ≤ 5 mm): ≥ 10 mm --\> longest diameter * Physical exam (using calipers): ≥ 10 mm * Lymph nodes by CT scan ≥ 15 mm --\> measured in short axis * All radiology studies must be performed within 21 days prior to registration (exception: within 28 days if negative). * Age ≥ 18 years. * ECOG performance status 0 or 1. Previous Therapy Cytotoxic Chemotherapy: * Patients must not have received prior chemotherapy for any stage of advanced/metastatic disease. * Patients who received previous (neo)adjuvant cisplatin-based systemic chemotherapy must have received the last dose of chemotherapy at least 12 months before registration. Please contact CCTG PRIOR to randomization for such patients. Other Anti-Cancer Therapy: * Patients may not have received targeted small molecule therapy, immunotherapies and viral therapies, biologic therapies and angiogenesis inhibitors for advanced/metastatic disease, or any prior immunotherapy for any stage of disease. Radiation: * Patients may have had prior radiation therapy, but NOT to the thorax unless clear disease progression has been demonstrated and confirmed with CCTG. A minimum of 28 days must have elapsed between the end of radiotherapy and registration onto the study. Radiation must have involved \< 30% of functioning bone marrow and there must be measurable disease outside the previously irradiated area (patients whose sole site of disease (for example pleural rind) is in a previously irradiated area are ineligible UNLESS there is evidence of progression, or new lesions have been documented, in the irradiated field). Please contact CCTG PRIOR to randomization if the patient has received prior thoracic radiation. Patients must have recovered from any acute toxic effects from radiation prior to registration. Previous Surgery: * Previous major surgery is permitted provided that it has been at least 28 days prior to patient registration and that wound healing has occurred. * Lab Requirements: * Absolute neutrophils ≥ 1.5 x 10\^9/L * Platelets ≥ 100 x 10\^9/L * Hemoglobin ≥ 90 g/L * Bilirubin ≤ 1.5 x ULN (upper limit of normal) * AST and ALT ≤ 2.5 x ULN * Serum creatinine \< 1.25 x ULN or Creatinine clearance ≥ 50 mL/min * Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. * Patients must be accessible for treatment, response assessment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. * In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient randomization. * Women/men of childbearing potential must have agreed to use two highly effective contraceptive methods during the study and for six months after discontinuation. * Patient must be able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires. Exclusion Criteria: * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at doses more than 10 mg prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first and any dose of trial treatment. * Has active autoimmune disease that has required systemic treatment in the past 3 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) or history of allogeneic transplantation. 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. * Must not have received a live vaccine within 30 days of planned start of study therapy. * Patients with 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. * Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction including cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects) or who have had unstable angina congestive heart failure or myocardial infarction within the previous year. Patients with a significant cardiac history, this includes hypertension, even if controlled, should have a LVEF ≥ 50%. * Patients with a history of other malignancies unless having undergone curative therapy (i.e. resection, radiation, etc) and do not require concurrent anticancer therapy. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or any of the other chemotherapy agents. * Concurrent treatment with other investigational drugs or anti0cancer therapy. * Patients with serious illness or medical condition that would not permit the patient to be managed according to the protocol including, but not limited to: * History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements. * Active infection requiring systemic therapy; (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) \[note: testing in asymptomatic patients is not required\] or tuberculosis). * Known history of, or any evidence of active, non-infectious pneumonitis. * Any other medical conditions that might be aggravated by treatment. * Serious or non-healing wound, ulcer, or bone fracture. * Patients with evidence of interstitial lung disease. * Patients with severe/uncontrollable tumor pain that requires radiation prior to starting on systemic therapy. * Pregnant or lactating women. (N.B.: All women of childbearing potential must have a negative pregnancy test within 72 hours prior to registration).