Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy

This study is testing whether analyzing small fragments of tumor DNA circulating in the blood can help doctors decide which type of immunotherapy (or combination) works best for patients with advanced non-small cell lung cancer (NSCLC). Researchers want to match patients to the most effective treatment based on a blood test result. **You may be eligible if...** - You are 18 or older with newly diagnosed Stage IV lung cancer (non-small cell type) that has not been treated yet - Your tumor tests positive for a protein called PD-L1 - You are well enough to carry out light daily activities (not bedridden) - Your blood counts and organ function (liver, kidneys) are within acceptable ranges - You are willing to have regular blood tests for circulating tumor DNA throughout the study **You may NOT be eligible if...** - Your lung cancer has a specific genetic driver mutation (EGFR, ALK, ROS1, MET, or RET) for which approved targeted drugs exist - You have untreated cancer spread to the brain - You have an active autoimmune disease requiring strong immune-suppressing medications - You have significant heart disease, active hepatitis B or C, or a life expectancy under 12 weeks Talk to your doctor to see if this trial is right for you.