Osimertinib and Locally Ablative Radiotherapy in Patients With Synchronous Oligo-metastatic EGFR Mutant NSCLC (STEREO)

- Histologically confirmed, treatment naïve EGFR-mutant NSCLC, with or without T790M resistance mutation. Presence of the sensitising EGFR-mutation (exon 19 deletion and/or exon 21 L858R) detected by an accredited laboratory.

- Synchronous oligo-metastatic stage IV disease (max 5 lesions)

- Measurable disease as defined according to RECIST v1.1

- All lesions amenable for radical radiotherapy according to local judgment

- Age ≥18 years

- ECOG performance status 0-2

- Life expectancy ≥12 months

- Adequate haematological, renal & liver function

- Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 7 days before enrolment.

- Written IC for protocol treatment

- Prior chemotherapy, immunotherapy, radiotherapy or therapeutical surgery for NSCLC (an exception is the resection and postoperative radiotherapy of the resection cavity of CNS or adrenal metastases)

- More than 5 distant oligo-metastases (any second intra-thoracic lesion will count as a distant metastasis; regional nodal metastases will not count towards 5 oligo-metastases) and more than 2 intra-thoracic lesions.

- Brain metastases not amenable for radiosurgery or neurosurgery

- Presence of leptomeningeal metastases

- Symptomatic spinal cord compression

- Extracranial metastatic locations not amenable for radical radiotherapy

- Currently receiving medications or herbal supplements known to be potent CYP3A4 inducers

- Any evidence of severe or uncontrolled systemic diseases

- 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

- Any of the following cardiac criteria: QTcF >470 msec; 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

- Past medical history of Interstitial Lung Disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD

- Idiopathic pulmonary fibrosis which is a contraindication to lung radiation.

- History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.

- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

- Women who are pregnant or in the period of lactation.

- Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the trial and up to 6 weeks for women and up to 4 months for men, after the last osimertinib dose.