Durvalumab (MEDI4736) With or Without SBRT in Clinical Stage I, II and IIIA Non-small Cell Lung Cancer

Inclusion Criteria

• Patient has histologically or cytologically proven clinical stages I (tumors > 2 cm), II, and IIIA NSCLC and is considered eligible for surgical resection with curative intent. Patients with 2 primary non-small cell lung cancers are allowed.
• Measureable disease, as defined by RECIST v1.1.
• Written informed consent and HIPAA obtained from the subject prior to performing any protocol-related procedures.
• Age > 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
• AST (SGOT)/ALT (SGPT), and alkaline phosphatase ≤ 2.5 x institutional upper limit of normal (ULN).
• Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• 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).

• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• No prior therapy for their lung cancer.

Exclusion Criteria

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

• Participation in another clinical study with an investigational product during the last 3 weeks.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥3 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, in-situ urinary bladder cancer , treated localized prostate cancer and ductal carcinoma-in situ.
• Indolent hematological malignancies
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal,inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, and steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Any unresolved toxicity (CTCAE grade 2) from therapy for a prior malignancy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel