Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.

Stage III non-small-cell lung cancer (NSCLC) patients account for about one-third of newly diagnosed NSCLC, with a large population and strong heterogeneity, posing significant challenges for clinical treatment. Concurrent chemoradiotherapy plus immune checkpoint inhibitors is the recommended therapeutic approach for patients with unresectable stage III non-small cell lung cancer (NSCLC), although surgery offers the chance of cure. However, existing evidence suggests that patients with driver mutation positive NSCLC have limited benefits from immunotherapy. There is still controversy over the definition of 'unresectable', and some stage IIIA and specific stage IIIB-N2 patients may also benefit from comprehensive surgical treatment. Emerging data supports the use of targeted therapies in NSCLC patients with a rare mutation. The aim of this umbrella study is to explore the efficacy of induction next generation sequencing (NGS)-directed targeted therapies followed by surgery for unresectable stage III NSCLC patients whose tumor harbors a rare mutation (Without EGFR Sensitizing Mutations).