This is a randomized, placebo-controlled, double-blind, multicenter, integrated phase II/III study.

Induction treatment
Patients will receive 4 cycles of cemiplimab monotherapy or in combination with platinum-doublet chemotherapy every 3 weeks
Post-induction treatment
At the end of the induction treatment, patients will enter the post-induction treatment phase, in which they will undergo disease assessment by imaging. Patients with PD after the induction treatment will be excluded. In case of clinical benefit (CR, PR or SD), patients will move to the next phase.
Radical therapy
Patients with PR and SD after the induction treatment will undergo radical treatment (definitive radiotherapy and/or surgery) of the primary tumour, the lymph nodes -if involved- and all detectable metastases.

Primary endpoint

Progression Free Survival according to RECIST 1.1 defined as the time interval from the date of randomization to the date of first occurrence of any of the following events:

• Disease progression at any site: loco-regional progression/recurrence (related to primary tumour); progression/recurrence of oligometastatic lesions initially present at registration
• Development of new metastatic lesions
• Death due to any cause

Patients alive and free of progression prior to the analysis cut-off date are censored at the date of the last disease assessment (before the cut-off date).

Secondary trial endpoints

• Overall survival
• Time to disease progression
• Time to development of new metastatic lesions
• Time to progression in oligometastatic lesions initially present at registration
• AEs according to NCI-CTCAE v5.0 and SAEs
• Patient-reported symptoms and treatment side-effects as measured by the EORTC QLQ-C30 and IL316 questionnaires.

Exploratory endpoints

• Prognostic value of ctDNA, immune profiles

• Histologic or cytologic confirmation of NSCLC. If small-cell elements present, participant will be ineligible.
• Synchronous oligometastatic disease at diagnosis – and still oligometastatic at registration into the study - defined as maximum 5 metastases, in maximum 3 organs. Hilar, mediastinal and/or supraclavicular lymph nodes are not considered as metastases.
• Measurable disease according to RECIST 1.1.
• Age at registration ≥18 years
• Eastern Cooperative Oncology Group performance status (ECOG PS)/ World Health Organization (WHO) 0-1

Hepatic function:

• Serum total bilirubin ≤1.5x upper limit of normal (ULN), or ≤3x ULN, if liver metastases or in patients with history of Gilbert syndrome
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤3x ULN (or ≤5x ULN, if liver metastases)

Renal function:

• Glomerular filtration rate (GFR) based on the modification of diet in renal disease (MDRD) equation ≥30 mL/min

Bone marrow function:

• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1.5 x 10^9/L
• Platelet count ≥100 x 10^9/L

• Presence of malignant pleural, pericardial and/or peritoneal effusion.
• Presence of leptomeningeal carcinomatosis.
• Tumour known to be positive for EGFR exon 19 or 21 mutations, ALK translocations or ROS1fusions.
• Prior pneumonectomy, radiotherapy (including mediastinal radiotherapy), chemotherapy,immune-check inhibitors or targeted therapy for lung cancer within the last 3 years beforeregistration.
• Previously treated brain metastases that are radiologically non-stable.

Notes:

• Patients with previously treated brain metastases, i.e., without evidence of progression for atleast 4 weeks by repeat imaging (note that the repeat imaging should be performed duringstudy screening), clinically stable and without requirement of steroid treatment for at least 14days prior to first dose of study intervention, can participate. These treated brain metastaseswill count as metastasis in the definition of oligometastatic disease.

• Symptomatic brain metastases should be treated with surgery and/or stereotacticradiotherapy/ radiosurgery as soon as possible after diagnosis. If surgery is considered it mustbe applied before enrolment. Radiotherapy can be performed at any time.

• History of any solid or haematological malignancy in the past 3 years before registration.
  Exceptions include patients who underwent successful definitive treatment of basal or squamouscell carcinoma of the skin, or any in-situ carcinoma(s).

• Any uncontrolled, intercurrent illness or clinical situation that would, in the judgment ofinvestigator, limit compliance with study requirements.

• Any uncontrolled active infection, defined as an infection ≥ grade 3 according to CTCAE version5.0.

• Any autoimmune disease that has required systemic treatment in the past 2 years (defined as anyuse of disease modifying agents, corticosteroids or immunosuppressive drugs).

Replacement therapy (e.g., thyroxine for hypothyroidism or insulin for type I diabetes) is notconsidered a form of systemic treatment.