A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination with Tremelimumab Therapy or MEDI4736 Monotherapy Versus Standard of Care Platinum-Based Chemotherapy in First Line Treatment of Patients with Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC) (MYSTIC)

- Histologically or cytologically documented Stage IV NSCLC with locally advanced disease not amendable to curative surgery or radiation. ;- Patients must have tumors that lack activating EGFR mutation and ALK rearrangement per local laboratory test.;- No prior chemotherapy or any other systemic therapy for locally advanced or metastatic NSCLC. Patients who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for locally advanced disease are eligible, provided that progression has occurred >6 months from last therapy. ;- Able to undergo a fresh tumor biopsy during screening or to provide an available tumor sample taken <3 months prior to screening. Tumor lesions used for fresh biopsies should not be target lesions, unless there are no other lesions suitable for biopsy. Fine needle aspirate specimens are not acceptable. ;- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrolment.;- At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as *10 mm in the longest diameter (except lymph nodes which must have a short axis *15 mm) with CT or MRI and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. ;- No prior exposure to immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.

- Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant ;- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. ;- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug;- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. ;- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, 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), Graves* disease, 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 vitiligo or alopecia;* Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment;9. Any condition that, in the opinion of the Investigator, would interfere with the evaluation of IP or interpretation of patient safety or study results, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from MEDI4736 or tremelimumab, or compromise the ability of the patient to give written informed consent;- No medical contraindication to platinum (cisplatin or carboplatin)-based doublet chemotherapy;- History of another primary malignancy except for ;Malignancy treated with curative intent and with no known active disease *5 years before the first dose of study drug and of low potential risk for recurrence;* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;* Adequately treated carcinoma in situ without evidence of disease (eg, cervical cancer in situ);- History of leptomeningeal carcinomatosis;- Brain metastases or spinal cord compression unless patient is stable (asymptomatic, no evidence of new or emerging brain metastases) and off steroids and anti-convulsants for at least 14 days prior to study treatment. - History of active primary immunodeficiency ;- Active infection including tubercolosis (clinical evaluation), hepatitis B, hepatitis C, or human immunodeficiency virus (HIV);- Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736 or tremelimumab. The following are exceptions to this criterion:;* Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection).;* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent;* Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication);- Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP.;- Female patients who are pregnant or breast-feeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of MEDI4736 + tremelimumab combination therapy or 90 days after the last dose of MEDI4736 monotherapy.;-Known allergy or hypersensitivity to IP or any excipient