We sought to investigate mechanisms of sensitivity and resistance to RET inhibitors in RET-fusion positive lung cancer....We characterized the landscape of RET-fusions and -mutations in non-small cell lung cancer (NSCLC)....In cells expressing the KIF5B-RET (K15, R12) fusion, the G810S mutation was associated with acquired resistance to both selpercatinib and pralsetinib, consistent with prior reports and clinical observations. However, V804M/E and M918T mutations were associated with acquired resistance to selpercatinib but not pralsetinib, and L730I/V and E732K mutations were associated with resistance to pralsetinib but not selpercatinib.