The phase I clinical trials of the pan-RAF inhibitor LY3009120 and LXH254 in advanced or metastatic cancers have been terminated because of their unfavorable efficiency.1016–1018 However, a phase I clinical trial of LXH254 in combination with LTT462 or trametinib or ribociclib for the treatment of KRAS or BRAF mutant NSCLC or NRAS mutant melanoma (NCT02974725) is ongoing.951 In addition, PLX8349 is an orally available, second-generation BRAF inhibitor with IC50 values of 3.8 nM, 14 nM, and 23 nM for BRAFV600E, BRAF, and CRAF, respectively. Here, RAF1 is linked to melanoma.