PALACE: Cemiplimab Trial According to ctDNA Levels

Inclusion Criteria: * Histologically confirmed stage IV or stage IIIB/C not candidates for definitive chemo/radiotherapy or surgical resection non-small cell lung cancer (NSCLC) per the 8th edition TNM with no prior systemic anti-cancer therapy * PDL1 ≥50% * ECOG performance status 0-1 * Patients aged ≥ 18 years * Prior adjuvant or neoadjuvant chemotherapy for early stage is permitted if completed at least 6 months prior to enrolment * Presence of at least one measurable lesion by CT-scan per RECIST version 1.1 * Anticipated life expectancy \>12 weeks * Correct hematological, hepatic and renal function * Patient consent must be obtained in the appropriate manner as established in the applicable local and regulatory requirements * Patients must be accessible for treatment and follow-up * Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 3 days before enrolment. * All sexually active men and women of childbearing potential must use a highly effective contraceptive method during the study treatment and for a period of at least 4 months following the last administration of trial drugs Exclusion Criteria: * Patients whose tumors harbor an activating mutation in EGFR, ALK translocation, or ROS Proto-Oncogene 1 (ROS1) rearrangements sensitive to available targeted inhibitor therapy * Patients with grade ≥2 neuropathy * Pregnant or breastfeeding women * Patients with a weight loss \>10% within the previous 3 months * Patients with carcinomatous meningitis * Patients with a history of other malignant diseases within the past 3 years * Patients must have recovered from a major surgery at least 14 days prior to enrolment * Patients with active or uncontrolled infections or with serious medical conditions or disorders that may not allow patient management as established in the protocol * Prior treatment with antineoplasic drugs or thoracic radiotherapy for any reason different from the ones specific in the inclusion criteria * Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemo-radiotherapy with curative intent for non-metastatic disease less than 6 months before enrollment since the last chemotherapy, radiotherapy, or chemo-radiotherapy * Patients with a combination of small cell lung cancer and non-small cell lung cancer, a carcinoid lung tumor or large cell neuroendocrine carcinoma * Has known allergy or hypersensitivity to components of study drug * Significant comorbidities that preclude the administration of chemotherapy according to the investigator's criteria * Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments * Untreated brain metastasis(es) that may be considered active * Immunosuppressive corticosteroid doses within 4 weeks prior to the first dose of cemiplimab * Uncontrolled infection with hepatitis B or hepatitis C or human immunodeficiency virus; or diagnosis of immunodeficiency * History of interstitial lung disease or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management. * History of documented allergic reactions or acute hypersensitivity reactions attributed to antibody treatments * Patients with a history of solid organ transplant * Receipt of live vaccines within 30 days of first study treatment * Women of childbearing potential, or sexually active men, who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment prior to the start of the first treatment, during the study, and for at least 4 months after the last dose.