Overview

This is an open-label, non-randomised, phase II, multicenter clinical trial. 63 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 will be enrolled in this trial to determine whether therapy decision making based on ctDNA analysis improves overall survival.

Eligibility

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.