A Study to Determine Safety of Durvalumab After Sequential Chemo Radiation in Patients With Unresectable Stage III Non-Small Cell Lung Cancer

Inclusion criteria: 1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 2. Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses. 3. Provision of signed and dated written genetic informed consent prior to collection of sample for genetic analysis (optional). 4. 18 years or older at the time of signing the ICF. 5. Histologically- or cytologically-documented NSCLC with locally-advanced, unresectable Stage III disease (according to the IASLC Staging Manual Version 8 \[IASLC 2016\]). Positron emission tomography (PET)/CT, MRI of the brain, and endobronchial ultrasound with biopsy are highly encouraged at diagnosis. 6. Receipt of sCRT which must have been completed within 42 days prior to first IP dose administration in the study. 1. The platinum-based chemotherapy regimen must contain cisplatin or carboplatin and 1 of the following agents: etoposide, vinblastine, vinorelbine, a taxane (paclitaxel or docetaxel), or pemetrexed, according to the local standard of care (SoC) regimens. Platinum-based chemotherapy containing cisplatin or carboplatin and gemcitabine is permitted under certain conditions - refer to bullet point 6(b). 2. Patients must have received at least 2 cycles of platinum-based chemotherapy before radiation therapy. The interval between administration of the last dose of chemotherapy regimen and start of radiation therapy must be no more than 6 weeks. Consolidation chemotherapy after radiation is not permitted. (i) If the patient's platinum-based chemotherapy contained gemcitabine, no overlap between chemotherapy and radiation therapy is permitted. (ii) If the patient's platinum-based chemotherapy contained any of the agents listed in (a) other than gemcitabine, an overlap of 1 cycle of chemotherapy and radiation therapy is acceptable. (c) Patients must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy). Sites are encouraged to adhere to mean organ radiation dosing as follows: (i) Mean lung dose \<20 Gy and/or V20 \<35%; (ii) Mean oesophagus \<34 Gy; (iii) Heart V45 \<35% or V30 \<30%. Note: Sites should be aware of the recent RTOG 0617 Study data demonstrating that doses higher than 60 Gy may be associated with greater toxicity and worse efficacy. (d) Patients with WHO/ECOG PS 2 or chronic lung disease (pulmonary emphysema or chronic obstructive pulmonary disease) must have received a V20 \<25%. 7. Patients must not have progressed following platinum-based sCRT, as per Investigator assessed RECIST 1.1 criteria. . In order to assess disease progression, the baseline imaging (CT/MRI) used for Screening purposes should be compared against the most recently performed scan that allows physician assessment as per RECIST 1.1 criteria. If an intermediate scan taken between chemotherapy and radiotherapy is available and that scan is suitable for physician assessment as per RECIST 1.1 criteria, then this scan should be used. 1. Patients with measurable disease and/or non-measurable and/or no evidence of disease (NED) assessed at baseline by CT/MRI will be entered in this study. 2. Prior irradiated lesions may be considered measurable and selected as TLs provided they fulfil the other criteria for measurability. 8. Must have a life expectancy of at least 12 weeks at enrolment. 9. WHO/ECOG PS ≤2. 10. Adequate organ and marrow function at enrolment as defined below. These parameters should be achieved without augmentation by growth factors, transfusions, or infusions within 14 days of screening unless required for SoC: 1. Haemoglobin ≥9.0 g/dL; 2. Absolute neutrophil count \>1.0 × 109/L; 3. Platelet count \>75 × 109/L; 4. Serum bilirubin ≤1.5 × upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician. 5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN. 6. Measured creatinine clearance \>40 mL/min or calculated creatinine clearance \>40 mL/min as determined by Cockcroft-Gault (using actual body weight) (Cockcroft and Gault 1976). Males: Creatinine clearance (mL/min) = Weight (kg) × (140 Age) 72 × serum creatinine (mg/dL) Females: Creatinine clearance (mL/min) = Weight (kg) × (140 Age) × 0.85 72 × serum creatinine (mg/dL) 11 Body weight \>30 kg at enrolment and first IP dose administration. 12 Male or female. 13 Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: 1. Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). 2. Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy). Exclusion criteria: 1. Patients with locally-advanced NSCLC whose disease has progressed following platinum based sCRT. 2. Patients who have disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumours. 3. Mixed small-cell lung cancer and NSCLC histology. 4. History of allogeneic organ transplantation. 5. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion: 1. Patients with vitiligo or alopecia. 2. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement. 3. Any chronic skin condition that does not require systemic therapy. 4. Patients without active disease in the last 5 years at enrolment may be included but only after consultation with the Study Physician. 5. Patients with celiac disease controlled by diet alone. 6. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, ILD, serious chronic GI conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent. 7. History of another primary malignancy except for: 1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence. 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. 3. Adequately treated carcinoma in situ without evidence of disease. 8. History of leptomeningeal carcinomatosis. 9. History of active primary immunodeficiency. 10. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive hepatitis B surface antigen \[HbsAg\] result), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies). Patients with a past or resolved hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HbsAg) are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). 11. Any unresolved toxicity of NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. 1. Patients with Grade ≥2 neuropathy or Grade ≥2 lymphopenia will be evaluated on a case-by-case basis after consultation with the Study Physician. 2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab (MEDI4736) may be included only after consultation with the Study Physician. 12. Known allergy or hypersensitivity to durvalumab (MEDI4736) or any of the IP excipients. 13. Patients who have received cCRT for locally-advanced NSCLC, or who received sCRT with at least 2 concomitant CRT cycles. Prior surgical resection (ie, Stage I or II) is permitted. Note: Patients whose platinum-based chemotherapy contained gemcitabine and who received sCRT with at least 1 concomitant CRT cycle are excluded from this study. 14. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine while receiving IP and up to 30 days after the last dose of IP. 15. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. 16. Prior exposure to immune-mediated therapy, including but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti PD L2 antibodies, excluding therapeutic anticancer vaccines. 17. Current or prior use of immunosuppressive medication within 14 days before the first dose of IP. The following are exceptions to this criterion: 1. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection); 2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; 3. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). 18. Previous IP assignment in the present study. 19. Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up period of an interventional study. 20. Participation in another clinical study with an IP during the 4 weeks prior to the first IP dose administration. 21. Prior randomisation or treatment in a previous durvalumab (MEDI4736) ± tremelimumab clinical study regardless of treatment arm assignment. 22. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of IP. 23. Judgment by the Investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements. 24. Genetic research study (optional): Exclusion criteria for participation in the optional (DNA) genetic research component of the study include: 1. Previous allogeneic bone marrow transplant. 2. Non-leukocyte-depleted whole blood transfusion in 120 days of genetic sample collection.