Effect of immunotherapy in patients with oligo-metastatic (limited number of metastases) non-small cell lung cancer after being treated with radiotherapy and/or surgery

Prior treatment

• Registration phase: Receipt of live vaccines (including attenuated) within 30 days of first study treatment.
• Registration phase: Participation in any other clinical study involving an investigational drug or device within 4 weeks before registration.
• At randomization: Use of immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 2 weeks prior to the first dose of cemiplimab/placebo. Patients who require brief courses of steroids (e.g., as prophylaxis for imaging studies due to hypersensitivity to contrast agents) can be included.
• Registration phase: History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or history of non-infectious pneumonitis that required systemic glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥12 months prior to registration.
• Registration phase: Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 2 weeks prior to the first dose of cemiplimab. Patients who require brief courses of steroids (e.g., as prophylaxis for imaging studies due to hypersensitivity to contrast agents) can be included.
• Registration phase: Prior pneumonectomy, radiotherapy (including mediastinal radiotherapy), chemotherapy, immune-check inhibitors or targeted therapy for lung cancer within the last 3 years before registration.
• Registration phase: Previously treated brain metastases that are radiologically non-stable.

Other illness

• Registration phase: Presence of malignant pleural, pericardial and/or peritoneal effusion.
• Registration phase: 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 squamous cell carcinoma of the skin, or any in-situ carcinoma(s).
• Registration phase: Any uncontrolled, intercurrent illness or clinical situation that would, in the judgment of investigator, limit compliance with study requirements.
• Registration phase: Any uncontrolled active infection, defined as an infection ≥ grade 3 according to CTCAE version 5.0.
• Registration phase: Any autoimmune disease that has required systemic treatment in the past 2 years (defined as any use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine for hypothyroidism or insulin for type I diabetes) is not considered a form of systemic treatment. The following treatments are allowed: • Intranasal, inhaled and topical steroids as well as local steroid injections (e.g., intra articular injection). • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. • Systemic corticosteroid replacement therapy for adrenal or pituitary insufficiency. • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Registration phase: History of documented allergic reaction or acute hypersensitivity reaction attributed to antibody treatments.
• Registration phase: Sensitivity to any of the study interventions, or components thereof, or other allergy that, in the opinion of the investigator, contraindicates participation in the study.
• Registration phase: Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol, understanding and completion of questionnaires and followup schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial
• Registration phase: Known active hepatitis B or C, defined as a positive HBV surface antigen (HBsAg) result or positive HCV RNA.
• Registration phase: Known active HIV infection, defined as >200 copies of HIV per ml of blood.

Lab values

• Registration phase: Tumour known to be positive for EGFR exon 19 or 21 mutations, ALK translocations or ROS1 fusions.

Other

• Registration phase: Presence of leptomeningeal carcinomatosis.

• Registration phase: Histologic or cytologic confirmation of NSCLC. If small-cell elements present, participant will be ineligible.
• Registration phase: Patients of childbearing / reproductive potential should agree to use adequate birth control measures, as defined by the protocol, during the study treatment period and for: • At least 6 months after the last dose of pemetrexed-if pemetrexed was administered. • At least 6 months after the last dose of cemiplimab/placebo.
• Registration phase: Women who are breast feeding should discontinue nursing prior to the first dose of study treatment and until: • At least 6 months after the last dose of pemetrexed, if pemetrexed was administered. • At least 6 months after the last dose of cemiplimab/placebo.
• Registration phase: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• At randomization: Stable disease, partial or complete response according to RECIST v.1.1 after 4 cycles of induction treatment and radical treatment of all residual disease (if applicable). Patients with progressive disease will be excluded.
• At randomization: Anticipated life expectancy >12 weeks
• At randomization: Hepatic function: • Serum total bilirubin ≤1.5x ULN (or ≤3x ULN, if liver metastases or in patients with history of Gilbert syndrome) • AST and/or ALT ≤3x ULN (or ≤5x ULN, if liver metastases)
• At randomization: Renal function: GFR based on MDRD equation ≥30 mL/min
• At randomization: Bone marrow function: • Haemoglobin ≥9.0 g/dL • ANC ≥1.5 x 10^9/L • Platelet count ≥100 x 10^9/L
• At randomization: WOCBP must have a negative serum or highly negative urine pregnancy test within 7 days prior to the first dose of consolidation treatment.
• Registration phase: De-novo oligometastatic disease at diagnosis (first-time diagnosis of oligometastatic disease): including synchronous oligometastatic disease and metachronous oligorecurrence (in patients who have never received any systemic treatment). Oligometastatic disease is defined as maximum 5 metastases, in maximum 3 organs. Hilar, mediastinal and/or supraclavicular lymph nodes are not considered as metastases.
• Registration phase: Measurable disease according to RECIST 1.1.
• Registration phase: Age at registration ≥18 years
• Registration phase: Eastern Cooperative Oncology Group performance status (ECOG PS)/ World Health Organization (WHO) 0-1.
• Registration phase: 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)
• Registration phase: Renal function: Glomerular filtration rate (GFR) based on the modification of diet in renal disease (MDRD) equation ≥30 mL/min
• Registration phase: Bone marrow function: • Haemoglobin ≥9.0 g/dL • Absolute neutrophil count (ANC) ≥1.5 x 10^9/L • Platelet count ≥100 x 10^9/L
• Registration phase: Women of childbearing potential (WOCBP) must have a negative serum or highly sensitive urine pregnancy test within 7 days prior to the first dose of treatment.