About the study

This is a Phase III, randomized, placebo-controlled, double-blind, multi-center study assessing the efficacy and safety of durvalumab with SoC SBRT versus placebo with SoC SBRT in patients with unresected clinical Stage I/II lymph node-negative (T1 to T3N0M0) NSCLC. An additional cohort will assess Osimertinib following SBRT in patients with early stage unresected T1 to T3N0M0 NSCLC harbouring an EGFR mutation.

Who can take part?

You may be eligible to participate in the study if you meet the following criteria:

Inclusion criteria

1. Age ≥18 years
2. Planned SoC SBRT as definitive treatment
3. WHO/ECOG PS of 0, 1 or 2
4. Life expectancy of at least 12 weeks
5. Body weight >30 kg
6. Submission of tumor tissue sample if available
7. Adequate organ and marrow function required
8. Patients with central or peripheral lesions are eligible
9. Staging studies must be done during screening (PET-CT within 10 weeks)
10. Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions Main Cohort Key

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
7. Age ≥18 years
8. Planned SoC SBRT as definitive treatment
9. World Health Organization (WHO)/ECOG PS of 0, 1, or 2
10. Patients with central or peripheral lesions are eligible
11. Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions
12. Staging studies must be done during screening (PET-CT within 10 weeks)
13. Submission of available tumor tissue sample
14. 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)
15. Adequate bone marrow reserve or organ function required
16. Female patients should be using highly effective contraceptive measures
17. 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
18. Mixed small cell and non-small cell cancer
19. Patients currently receiving potent inducers of CYP3A4
20. Patients with known or increased risk factor for QTc prolongation
21. Treatment with any of the following:
22. Preoperative or adjuvant platinum-based or other chemotherapy for the disease under investigation
23. Prior treatment with neoadjuvant or adjuvant EGFR TKI
24. 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
25. 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
26. Any of the following cardiac criteria
27. Mean resting corrected QT interval >470 msec, obtained from 3 ECGs
28. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
29. 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
30. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD

For a full list of inclusion/exclusion criteria, please visit ClinicalTrials.gov

Study locations

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How to apply

Determine if a study site for this clinical trial is near you. Contact the study to apply.