Immunotherapy, Chemotherapy, Radiotherapy and Surgery for Synchronous Oligo-metastatic NSCLC

Inclusion Criteria:

* Histologically confirmed non-small cell lung cancer
* Synchronous oligo-metastatic stage IV disease: maximum of three distant metastases, one of which must be extra-cerebral for stereotactic body radiotherapy (SBRT); Initial mediastinal staging is recommended (except for lymph nodes \<1 cm on CT and PET-negative) preferentially by endobronchial ultrasound (EBUS); Neurosurgical resection of one single central nervous system (CNS) metastasis or laparoscopic resection of one adrenal metastasis before study inclusion is allowed (one extra-cerebral metastasis must be available for SBRT)
* Able to understand and give written informed consent and comply with study procedures
* Age ≥18 years
* ECOG Performance Status 0-1
* Availability of tumour tissue for translational research
* Adequate haematological, renal and liver function

Exclusion Criteria:

* Prior chemotherapy, radiotherapy or therapeutic surgery for NSCLC (an exception is the resection of one single CNS or adrenal metastasis, as above)
* Activating driver mutation: epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), proto-oncogene receptor tyrosine kinase (ROS1)
* More than three distant metastases
* Brain metastases not amendable for radiosurgery or neurosurgery
* Extracranial metastatic locations such as malignant ascites, pleural or pericardial effusion, diffuse lymphangiomatosis of skin or lung, diffuse bone marrow metastasis, abdominal masses/abdominal organomegaly, identified by physical exam that is not measurable by reproducible imaging techniques.
* Primary lung cancer not suitable for radical therapy (pneumonectomy excluded)
* History of leptomeningeal carcinomatosis
* Major surgery or significant traumatic injury from which the patient has not recovered at least 28 days before enrolment
* Any uncontrolled intercurrent illness, including but not limited to: ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease or serious chronic gastrointestinal conditions associated with diarrhea, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol
* Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc) at screening.
* Known positivity for human immunodeficiency virus (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice)
* Active autoimmune disease requiring systemic treatment
* Severe or uncontrolled cardiac disease requiring treatment
* History of active primary immunodeficiency
* History of allogeneic organ transplant
* Receipt of live attenuated vaccines within 30 days prior to enrolment
* Known allergies or hypersensitivity to trial drugs or to any excipient.
* Women who are pregnant or in the period of lactation.
* Sexually active men and women of childbearing potential who are not willing to use a highly effective contraceptive method during the trial and up to 90 days after last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab and tremelimumab combination therapy