CISPLATIN for Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- 1. The participant (or legally acceptable representative) has provided documented informed consent to participation to the study and data protection consent form.\n- 2. Male or female aged 18 years or older.\n- 3. ECOG Performance Status of 0 – 2.\n- 4. Pathologically (histologically or cytologically) confirmed diagnosis of stage IV NSCLC (TNM 8th edition), who received no prior systemic treatment for recurrent or metastatic NSCLC. Mixed squamous/non-squamous tumors are eligible.\n- 5. PD-L1 TPS ≥ 50% (by local test).\n- 6. Absence of targetable oncogene alterations (EGFR, ALK, ROS1).\n- 7. Circulating CD10- LDNs >30.5% at screening. LDNs will be defined as CD11b+CD15+ cells among live PBMC. Flow cytometry raw data will be centrally analyzed by the coordinating center.\n- 8. Measurable disease (RECIST 1.1) on two CT scans performed before randomization. The following criteria must be fulfilled: - Participants must have at least one measurable lesion that has not been previously treated with radiotherapy. - Chest scans are mandatory, while chest and abdomen CT scans are preferred. - Availability of measurable disease scans to be anonymized and sent for central independent confirmation by a radiologist of the coordinating center. - A minimum 2-week interval and a maximum 12-week interval will be acceptable between the two pre-treatment CT scans. - Availability to perform the baseline scan within a maximum 4-week interval before treatment start.\n- 9. Patient’s willingness to undergo blood draws to provide plasma and blood samples for analysis according to study objectives.\n- 10. Adequate organ and marrow function as defined below: - Absolute neutrophil count > 1.5 x 109/L (1500/mm3) - Platelets ≥100 x 109/L (100 000/mm3) - Haemoglobin ≥9.0 g/dL (5.59 mmol/L) - Adequate renal function: Calculated creatinine clearance (according to Cockroft-Gault): ≥60ml/min for patient receiving cisplatin; ≥45ml/min for patient receiving carboplatin. - Serum bilirubin ≤1.5 x upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of hemolysis or hepatic pathology) who will be allowed in consultation with their physician. - AST and ALT ≤2.5 x ULN.\n- 11. Absence of a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents and/or cemiplimab and/or to any of their excipients"}

Exclusion criteria

• {"criterion_text":"- 1. Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication 2. Known uncontrolled infection with HIV, hepatitis B or hepatitis C infection, diagnosis of immunodeficiency, and/or tuberculosis (active or latent). No serological testing is required unless mandated by local health authority. 3. Administration of live or live-attenuated vaccines within 30 days before the baseline LDNs assessment. Administration of killed vaccines is allowed. Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication. 4. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management. 5. Administration of radiotherapy within 7 days prior to the baseline LDNs assessment. 6. Administration of colony-stimulating factors (e.g., G-CSF, GM-CSF) or recombinant erythropoietin within 28 days prior to the baseline LDNs assessment. Primary prophylaxis with G-CSF and pegylated G-CSF is not allowed. Secondary prophylaxis is not recommended and required case-by-case discussion with the coordinator center before G-CSF administration. 7. Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments. The following are not exclusionary: vitiligo, childhood asthma that has resolved, endocrinopathies (such as hypothyroidism or type 1 diabetes) that require only hormone replacement, or psoriasis that does not require systemic treatment. 8. Female patients who are pregnant, breast-feeding, male, or female patients of reproductive potential who are not employing an highly effective method of birth control. 9. Any condition that, in the opinion of the investigator, would interfere with the evaluation of the study drug or interpretation of patient safety or study results. 10. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment (Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable). 11. Allogenic tissue/solid organ transplant."}

Primary endpoints

• {"endpoint_text":"- HPD and ED rate, defined as the proportion of patients with a delta of TGR ≥50% or a TGR ratio ≥2 at 7 weeks ± 5 days from randomization or who died before with no scan performed from treatment start","definition_or_measurement_approach":"Defined as the proportion of patients with a delta of tumor growth rate (TGR) ≥50% or a TGR ratio ≥2 at 7 weeks ± 5 days from randomization, or patients who died before with no scan performed from treatment start."}

Secondary endpoints

• {"endpoint_text":"- (related to activity-efficacy secondary objective) HPD rate, defined as the proportion of patients with a delta of TGR ≥50% and/or a TGR ratio ≥2 at 5 weeks ± 5 days from treatment start.","definition_or_measurement_approach":"Defined as proportion of patients with delta of TGR ≥50% and/or TGR ratio ≥2 at 5 weeks ± 5 days from treatment start."}
• {"endpoint_text":"- (related to activity-efficacy secondary objective) Objective Response Rate (ORR), defined as the percentage of patients with an objective response as determined by RECIST 1.1.","definition_or_measurement_approach":"ORR defined as percentage of patients with objective response per RECIST 1.1."}
• {"endpoint_text":"- (related to activity-efficacy secondary objective) Progression free survival (PFS), defined as the time from randomization to the date of first progression or death from any cause, whichever comes first. Data from patients who have not had an event at the time of data analysis will be censored on the date on which they are last known to be alive and event free.","definition_or_measurement_approach":"PFS measured from randomization to first documented progression or death; censoring at last known alive and event free."}
• {"endpoint_text":"- (related to activity-efficacy secondary objective) Overall survival (OS), defined as the time from randomization until the date of death from any cause. Data from patients who are still alive at the time of data analysis will be censored on the date on which they are last known to be alive.","definition_or_measurement_approach":"OS measured from randomization to death from any cause; censoring at last known alive date."}
• {"endpoint_text":"- (related to safety and tolerability secondary objective) Summary of adverse events (AE), with a focus on TRAEs coded based upon the Medical Dictionary for Regulatory Activities (MedDRA) and graded based upon CTCAE, ver. 5.0.","definition_or_measurement_approach":"AEs coded by MedDRA and graded by CTCAE v5.0; summary statistics reported with focus on treatment-related adverse events (TRAEs)."}
• {"endpoint_text":"- (related to exploratory objective) Characterization of clinical, radiological, and biological patients’ features correlated with HPD occurrence. -\tDynamic assessment of circulating and tissue features of HPD according to treatment type (cemiplimab alone or cemiplimab + PCT) -\tHPD rate among patients not meeting inclusion criterion 7 (circulating CD10- LDNs >30.5% at screening).","definition_or_measurement_approach":"Exploratory characterization of clinical, radiological and biological features; dynamic assessments of circulating/tissue features by treatment arm; subgroup HPD rate among patients not meeting biomarker inclusion criterion 7."}

Other endpoints

• {"endpoint_text":"- Characterization of clinical, radiological, and biological patients’ features correlated with HPD occurrence. - Dynamic assessment of circulating and tissue features of HPD according to treatment type (cemiplimab alone or cemiplimab + PCT) - HPD rate among patients not meeting inclusion criterion 7 (circulating CD10- LDNs >30.5% at screening).","definition_or_measurement_approach":"Exploratory analyses to characterize features correlated with HPD; dynamic assessment of circulating/tissue biomarkers by treatment arm; analysis of HPD rate in biomarker-negative patients."}

Italy

Earliest CTIS Part Ii Submission Date

28-01-2026

Latest Decision Or Authorization Date

10-02-2026

Processing Time Days

13

Number Of Sites

23

Number Of Participants

700

Primary sponsor

Full Name

Universita' Vita-salute S. Raffaele

Organisation Type

Educational Institution

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Istituto Di Ricerche Farmacologiche Mario Negri","duties_or_roles":"codes: 1,10,11,12,14,5,6,7,8","organisation_type":"Laboratory/Research/Testing facility"}