78TiP Clinical evaluation of NVL-520, a highly selective ROS1 inhibitor in patients with advanced ROS1-positive solid tumors: The phase I/II ARROS-1 study

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Oncogenic ROS1 gene rearrangements are implicated in the pathogenesis of various adult and pediatric cancers, including up to 3% of non-small cell lung cancers (NSCLC), where up to 40% of patients present with central nervous system (CNS) metastases. Tyrosine kinase inhibitors (TKIs) approved by the FDA and EMA for ROS1-positive NSCLC (crizotinib and entrectinib) are limited by acquired resistance, frequently mediated by secondary ROS1 kinase domain mutations. In addition, dual TRK/ROS1 kinase inhibitors, including entrectinib, are associated with neurologic adverse events.