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

Inclusion criteria

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
• Provision of signed and dated written genetic informed consent prior to collection of sample for genetic analysis (optional).
• 18 years or older at the time of signing the ICF.
• 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.
• Receipt of sCRT which must have been completed within 42 days prior to first IP dose administration in the study.
• 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).
• 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 1.0 × 109/L;

• Platelet count >75 × 109/L;
• 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.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.
• 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:

• Women 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

• Patients with locally-advanced NSCLC whose disease has progressed following platinum based sCRT.
• Patients who have disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumours.
• Mixed small-cell lung cancer and NSCLC histology.
• History of allogeneic organ transplantation.
• 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