P03.04 Phase II Study of TKIs as Neo(adjuvant) Therapy in Stage II–III Resectable NSCLC with ALK, ROS1, NTRK or BRAFV600 Alterations

Despite complete surgical resection, cure rates remain unacceptable in early-stage NSCLC. Trials of neoadjuvant and adjuvant chemotherapy have demonstrated a 5-year overall survival benefit 5% for patients with resectable disease. Developing new treatment strategies to increase cures following resection is critical this patient population. There are numerous immunotherapy trials ongoing the setting While there few targeted therapy genetic alterations, therapies remained incompletely explored potentially Neoadjuvant allow early trial read outs vivo efficacy assessment, which can guide options. The use lung cancers driver mutations has potential improve outcomes provide an alternative modality beyond chemotherapy. Tyrosine kinase inhibitors (TKIs) hypothesized greater clinical more favorable safety profile than current standard care platinum-based setting. This Phase II umbrella study (ML41591) designed determine stage II–III NSCLC ALK, ROS1, NTRK or BRAFV600 alterations. ML41591 II, multicenter, non-randomized, open-label, IIIA, selected IIIB tumors that harbor fusions missense mutation. therapies, investigate surrogate biomarkers response. Patients will be enrolled assigned within appropriate cohort: - ALK gene rearrangements alectinib ROS1 entrectinib NTRK1/2/3 BRAF mutation vemurafenib plus cobimetinib. Each cohort enroll approximately 25 patients. conducted two parts: pre-surgery evaluate pathologic response TKIs each cohort. who undergo surgery whose lack radiographic progression enter post-surgery surveillance phase, includes follow-up survival. portion exploratory. receive 4 cycles followed by as up 24 months. primary objective major pathological rate treatment, defined ?10% residual viable tumor cells specimens. Secondary objectives include investigator-assessed response, disease-free survival, event-free circulating-tumor DNA clearance rate. also exploratory pre- post-treatment tissue blood their correlation outcomes. Induction, Neoadjuvant, Adjuvant