Selpercatinib and capmatinib combination promotes sustained complete response in novel ISOC1-RET fusion lung cancer after resistance to RET inhibitor via MET amplification: Case Report.

fusions occur in 1-2% of non-small cell lung cancer. Selpercatinib and pralsetinib are selective inhibitors with significant improvement of outcome in patients with tumor harboring fusion; however, resistance mechanisms appear frequently, mainly driven by MAPK pathway bypass, secondary mutations, or in 5% via amplification. Co-inhibition of and is a compelling strategy for overcoming -dependent resistance to inhibitors and potentially other inhibitors. To our knowledge, this is the first report of a novel fusion lung cancer with a durable complete response to selpercatinib, with resistance via amplification, which was overcome by the successful combination of selpercatinib and capmatinib.