A ctDNA-guided Phase II Trial of Osimertinib in Combination With Sacituzumab Tirumotecan in EGFR-mutated Advanced NSCLC Patients With Positive ctDNA After lead-in Osimertinib Monotherapy

This study is testing whether combining osimertinib (a targeted lung cancer drug) with sacituzumab tirumotecan (an antibody-drug conjugate) can produce better results for people with EGFR-mutated advanced non-squamous lung cancer whose circulating tumor DNA (ctDNA) in blood remains detectable after starting osimertinib alone — suggesting a higher risk of early resistance. **You may be eligible if...** - You are 18 or older - You have been diagnosed with advanced (stage IIIB–IV) non-squamous non-small cell lung cancer with an EGFR mutation (exon 19 deletion or L858R) - You have completed 3 weeks of first-line osimertinib monotherapy and your cancer has not progressed - You have had a blood test (ctDNA test) and are either positive (Cohort 1) or negative (Cohort 2) - You are in good physical condition (ECOG 0–1) - Your blood counts, liver, kidney, and heart function are within required ranges **You may NOT be eligible if...** - Your lung cancer has squamous cell components or is small-cell type - You have active or symptomatic brain metastases - You have previously received chemotherapy or other systemic treatments for advanced lung cancer other than osimertinib - You have been treated with TROP2-targeted therapy before - You have serious heart or cardiovascular conditions within the past 6 months - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.