Durvalumab with stereotactic body radiation therapy (SBRT) vs placebo with SBRT in early stage unresected non-small cell lung cancer (NSCLC) patients/ Osimertinib following SBRT in patients with early stage unresected NSCLC harboring an EGFR mutation - PACIFIC-4

Exclusion Criteria

• 1. Mixed small cell and non-small cell cancer
• 2. History of allogeneic organ transplantation
• 3. History of another primary malignancy with exceptions
• 4. History of active primary immunodeficiency
• 5. Epidermal growth factor receptor local testing is strongly recommended prior to enrollment. Patients with a tumor harboring an EGFRm per local testing will be excluded from the main cohort
• 6. Prior exposure to immune-mediated therapy with exceptions
• Osimertinib Cohort Key Inclusion Criteria
• 1. Age ≥18 years
• 2. Planned SoC SBRT as definitive treatment
• 3. WHO/ECOG PS of 0, 1, or 2
• 4. Patients with central or peripheral lesions are eligible
• 5. Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions
• 6. Staging studies must be done during screening (PET-CT within 10 weeks)
• 7. Submission of tumor tissue sample if available
• 8. Confirmation by local laboratory that the tumor harbors one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R)
• 9. Adequate bone marrow reserve or organ function required
• 10. Female patients should be using highly effective contraceptive measures
• 11. Male patients should be asked to use barrier contraceptives (ie, condoms) during sex with all partners during the trial and avoid procreation
• Osimertinib Cohort Key Exclusion Criteria
• 1. Mixed small cell and non-small cell cancer
• 2. Patients with known or increased risk factor for QTc prolongation
• 3. Treatment with any of the following:
• -Preoperative or adjuvant platinum-based or other chemotherapy for the disease under investigation
• -Prior treatment with neoadjuvant or adjuvant EGFR TKI
• -Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4
• 4. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib
• 5. Any of the following cardiac criteria
• -Mean resting corrected QT interval >470 msec, obtained from 3 ECGs
• -Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
• -Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained -sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval
• -Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD