Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic Squamous or Non-Squamous NSCLC

Inclusion Criteria: * Patients must have histologically and/or cytologically confirmed diagnosis of squamous or non-squamous, non-small cell carcinoma of the lung. Patients with poorly differentiated tumours will only be eligible if NSCLC is confirmed by immunohistochemistry markers (TTF1/P63 or P40/CK5). Patients with known sensitizing EGFR mutations or known ALK-fusion are not eligible. * Patients must have stage IV disease according to the 8th TNM version staging. * Patients must have an adequate histopathology specimen and must consent to release this specimen for protocol required testing. This is a mandatory component of the study. * Patient must consent to provision of samples of blood in order that the specific correlative marker assays proscribed may be conducted. * All patients must have measurable disease as defined by RECIST 1.1 All radiology studies must be performed within 28 days prior to randomization (within 35 days if negative). The criteria for defining measurable disease are 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 Measurable lesions must be outside a previous radiotherapy field if they are the sole site of disease, unless disease progression has been documented. * Patients must be 18 years of age or older. * ECOG performance status of 0 or 1. * Absolute neutrophils ≥ 1.5 x 10\^9/L * Platelets ≥ 100 x 10\^9/L * Hemoglobin ≥ 90 g/L * Bilirubin ≤ 1.5 x UNL (upper limit of normal) * AST and ALT ≤ 2.5 x UNL (if liver metastases are present, ≤5 x UNL) Creatinine \< 1.25 UNL or Creatinine clearance ≥ 45 mL/min * Cytotoxic Chemotherapy: Patients may not have received prior cytotoxic chemotherapy for advanced/metastatic disease. * Adjuvant Chemotherapy: Patients may have had prior adjuvant therapy for completely resected disease, providing it has been completed at least 12 months prior to randomization. * Patients treated with concurrent chemotherapy/radiation regimens for unresectable locally advanced Stage III disease will be eligible providing it has been completed at least 12 months prior to randomization. * Other Systemic Therapy: Patients may not have received prior EGFR or alk inhibitors. Patients may not have received prior treatment with immune-based therapy, including durvalumab and tremelimumab vaccines or oncolytic viral therapy. Patients must have recovered from any reversible treatment related toxicities prior to randomization. * Prior external beam radiation is permitted provided a minimum of 14 days (2 weeks) have elapsed between the last dose of radiation and date of randomization. Concurrent radiotherapy is not permitted. Patients must have recovered from any acute toxic effects from radiation prior to randomization. * Patients must have recovered from any acute toxic effects from radiation prior to randomization. * Surgery: Previous surgery is permitted provided that wound healing has occurred and at least 14 days have elapsed (major surgery) prior to randomization. * Patient must be able (i.e. sufficiently fluent) and willing to complete the quality of life and health economics questionnaires. * Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. * Patients must be accessible for treatment and follow-up. All randomized patients must be followed and treated at participating centres. * In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient randomization. * Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception while on study and for 6 months after the last dose of durvalumab and tremelimumab or for 3 months after the last dose of durvalumab alone Exclusion Criteria: * Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 3 years. Patients with a history of other malignancies detected at an early stage and whom the investigator believes have been curatively treated and are at low risk of recurrence MAY be eligible. Contact CCTG to discuss eligibility prior to enrolling. * Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: * Patients with alopecia. * Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years). * Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement. * History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization\* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction. * Live attenuated vaccination administered within 30 days prior to randomization * History of hypersensitivity to durvalumab or tremelimumab or any excipient. Patients who have received other treatment or other antibodies must not have had intolerable toxicity or required steroids to manage toxicity. * Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome. * Patients who have untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if now controlled, should have a LVEF ≥ 45%. (Note: patients with uncomplicated controlled hypertension do not require LVEF measurement in the absence of other significant cardiac history) * Concurrent treatment with other investigational drugs or anti-cancer therapy * Patients with untreated brain or meningeal metastases are not eligible. Patients with treated CNS disease who have radiologic AND clinical evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to randomization). * Pregnant or Lactating Women: Women of childbearing potential must have a pregnancy test (urine or serum) proven negative within 14 days prior to randomization. If urine test is positive, pregnancy testing may then include an ultrasound to rule-out pregnancy if a false-positive is suspected. For example, when beta-human chorionic gonadotropin is high and partner is vasectomized, it may be associated with tumour production of hCG, as seen with some cancers. Patient will be considered eligible if an ultrasound is negative for pregnancy. Men and women of child-bearing potential must agree to use adequate contraception. * Patients with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol (including corticosteroid administration), or would put the patient at risk. This includes but is not limited to: * Contraindications to the use of pemetrexed, gemcitabine, cisplatin and/or carboplatin (consult product monograph); * 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) or tuberculosis); * Active peptic ulcer disease or gastritis; * Known pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function.