Efficacy and Safety of Ensartinib in Neoadjuvant Therapy for Stage IIA - IIIB (Operable or Potentially Operable) ALK-Positive Lung Adenocarcinoma ：A Multicenter, Real-World Clinical Study

According to the Global Cancer Statistics 2022 report, lung cancer is the most common type of cancer (12.4% of the total) and the leading cause of cancer deaths (18.7% of total cancer deaths). The statistics of the National Cancer Center of China shows that there are about 1 061 thousand new cases and 733 thousand deaths of lung cancer in China every year, which account for the first incidence and mortality of malignant tumors in China. According to the pathological classification of patients, lung cancer is divided into small cell lung cancer and non-small cell lung cancer, of which non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer. Surgery is the preferred treatment for patients with early-stage lung cancer, according to the 2024 CSCO Guidelines. However, most patients have the possibility of recurrence and metastasis after surgery. The 5-year survival rate of patients with stage IA NSCLC is 80%-90%, but the 5-year survival rate of patients with stage ⅢB NSCLC drops to 40%. Neoadjuvant therapy has become an important part of the treatment of non-small cell lung cancer (NSCLC) in order to prolong the survival of patients. In the past few years, many driver genes of NSCLC have been identified, and anaplastic lymphoma kinase (ALK) is one of them. ALK was first identified in anaplastic large cell lymphoma (ALCL). Studies at home and abroad have shown that ALK-rearranged (positive)NSCLC accounts for about 3%-7% of all NSCLC patients. Many studies such as The SAKULA study,The ALNEO Study have suggested that ALK-TKI is clinically feasible as a neoadjuvant therapy for ALK positve patients with locally advanced NSCLC. Ensartinib is a novel potent and highly selective second-generation ALK inhibitor, which has a good selective inhibition effect on c-Met. Structurally, Ensartinib is similar to crizotinib, but Ensartinib has stronger binding to ALK and better selectivity than crizotinib, and both in vitro and in vivo experiments have shown the potential of ensartinib for crizotinib-resistant tumors. The safety profile of ensartinib was manageable. In the eXalt3 study, the most common adverse events of all grades in the ensartinib group were rash, pruritus, and elevated aminotransferase (ALT, AST). The eXalt3 study confirmed that first-line use of ensartinib can significantly improve mPFS compared with crizotinib in ALK-positive NSCLC patients, and ensartinib provides better efficacy and safety, making it a new first-line treatment option for ALK-positive NSCLC patients. ALK inhibitors have brought great survival benefits to ALK-positive advanced NSCLC, but the exploration of ALK inhibitors in early-stage patients has just begun,with no authoritative results have been published. TThe investigators designed this study to explore the efficacy of neoadjuvant treatment with ensartinib in patients with stage IIA-IIB ALK-positive lung adenocarcinoma who had undergone neoadjuvant chemotherapy for ALK mutation. The primary goal of this study is to evaluate the major pathological response (MPR) to neoadjuvant ensartinib in patients with resectable stage IIA to IIIb ALK-positive non-small cell lung cancer (NSCLC). The secondary objectives are to evaluate the complete pathological response (pCR), objective response rate (ORR), and safety of neoadjuvant ensartinib in patients with resectable stage IIA-IIIb ALK-positive non-small cell lung cancer (NSCLC)