A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab with Stereotactic Body Radiation Therapy (SBRT) for the Treatment of Patients with unresected Stage I/II, lymph-node negative Non-small Cell Lung Cancer (PACIFIC-4/RTOG-3515) - PACIFIC-4/RTOG-3515

INTERVENTION: Product Name: durvalumab Product Code: MEDI4736 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Durvalumab CAS Number: 1428935‐60‐7 Current Sponsor code: MEDI4736 Other descriptive name: MEDI4736 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Solution for injection/infusion Route of administration of the placebo: Intravenous use CONDITION: Patients with unresected Stage I/II, lymph‐node negative Non‐small Cell Lung Cancer ; MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non‐small cell lung cancer System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: ; Secondary Objective: To assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS for all stage I/II NSCLC patients; To assess the efficacy of durvalumab monotherapy compared to placebo in terms of OS; To further assess the efficacy of durvalumab monotherapy compared to placebo in terms of lung cancer‐specific mortality; To further assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS24, TTP, TTDM, and PFS2; To assess the PK of durvalumab; To investigate the immunogenicity of durvalumab; To assess symptoms and health‐related quality of life in patients treated with durvalumab monotherapy compared to placebo using the EORTC QLQ‐C30; To assess the safety and tolerability profile of durvalumab monotherapy compared to placebo after administration of SBRT; Main Objective: To assess the efficacy of durvalumab monotherapy compared to placebo in terms of PFS in patients with T1c to T3N0M0 NSCLC Primary end point(s): PFS in patients with T1c to T3N0M0 NSCLC by BICR according to RECIST 1.1 Timepoint(s) of evaluation of this end point: On‐study tumor assessments occur 8 weeks after randomization, then every 12 weeks through week 116, then every 16 weeks through 3 years after randomization, then every 6 months thereafter until objective disease progression. SECONDARY OUTCOME: ; Secondary end point(s): PFS in patients with T1 to T3N0M0 NSCLC ; OS in patients with T1c to T3N0M0 NSCLC ; OS in patients with T1 to T3N0M0 NSCLC ; Lung cancer mortality ; PFS24, TTP, and TTDM using BICR assessments according to RECIST 1.1 ; PFS2 using local assessment ; Concentration of durvalumab in blood ; Presence of ADA for durvalumab ; EORTC QLQ‐C30: Change in symptoms, functioning, and global health status/quality of life ; Safety and tolerability: AEs, physical examinations, vital signs, electrocardiograms, and laboratory findings; ; Timepoint(s) of evaluation of this end point: OS: from baseline to until death due to any cause ; PFS24 ‐ at 24 months following randomization, TTP, TTDM: tumor assessments occur up to every 8 weeks 3 years after randomization, and then every 6 months thereafter ; Concentration of durvalumab in blood: at Week 4, 28, 52, 76 and week 100 and 3 Months after completed/discontinued study treatment ; ADA: will be collected at Baseline, at Week 28, 52, 76, 100 then months 3 and 6 after completed/discontinued study treatment ; EORTC QLQ‐C30: Screening, at Baseline, Week 2, 4, 6, 8, 12, 16 and 20 weeks after randomization, then every 8 weeks until 3 years after randomization, then every 6 months until PFS2 ; Safety and tolerability ‐ from randomization until 3 months after treatment discontinuation; INCLUSION CRITERIA: 1. Age =18 years 2. Histologically or cytologically documented Stage I to II NSCLC, with clinical Stage I/II lymph node‐negative (T1 to T3N0M0) disease and planned to receive definitive treatment with SBRT. Patients may be medically inoperable or are medically operable and refusing surgery or choosing to have SBRT (Stereotactic Body Radiation Therapy) as definitive therapy 3. Completion of SoC SBRT as definitive treatment prior to randomization 4. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) PS of 0, 1, or 2 5. Life expectancy of at least 12 weeks 6. Body weight >30 kg 7. Tumor sample required 8. Adequate organ and marrow function required 9. Patients with central or peripheral lesions are eligible 10. Staging studies must be done within 8 w