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Immune checkpoint inhibitors combined with platinum-based chemotherapy have become the first-line backbone for advanced, driver-negative non-small cell lung cancer (NSCLC), delivering meaningful survival gains; yet for most, disease control ultimately erodes, making immunotherapy resistance one of the most pressing unmet needs. To date, primary resistance to chemoimmunotherapy is defined as Response Evaluation Criteria in Solid Tumours (RECIST) progression within 6 months of treatment initiation after a minimum exposure of 6–8 weeks (approximately two cycles of the immunotherapy component); conversely, secondary resistance is defined as RECIST progression beyond 6 months in patients who have received >6 months of therapy.1