lifirafenib + mirdametinib

This combination therapy consists of **lifirafenib**, a small molecule RAF dimer inhibitor developed by BeiGene, and **mirdametinib**, an oral, allosteric small molecule MEK1/2 inhibitor developed by SpringWorks Therapeutics. Both drugs are administered orally and are being co-developed for the treatment of advanced or refractory solid tumors harboring MAPK pathway aberrations, including RAS and RAF mutations. Lifirafenib targets RAF family kinases as well as EGFR, while mirdametinib targets MEK1/2; by inhibiting different nodes in the MAPK/ERK pathway, the combination aims to block cancer cell signaling more effectively and overcome resistance that may develop to single agents. Clinically, the combination has shown encouraging objective response rates with a tolerable safety profile in phase 1b/2 trials in tumors with BRAF, KRAS, and NRAS mutations, including notable activity in low-grade serous ovarian cancer, non-small cell lung cancer, and endometrial cancer[1][2][3][4][5][7].