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

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.