BI 1701963 + trametinib

**BI 1701963 + trametinib** is a combination therapy under investigation for advanced solid tumors harboring KRAS mutations. BI 1701963 is a small-molecule inhibitor targeting the protein–protein interaction between KRAS and its guanine nucleotide exchange factor SOS1, thereby inhibiting the activation of KRAS by preventing the exchange of GDP for GTP. This inhibition suppresses KRAS-driven signaling and cell proliferation[3][5]. Trametinib, marketed as Mekinist, is a MEK inhibitor that blocks MEK1 and MEK2 activity in the MAPK pathway downstream of KRAS, contributing to further inhibition of cancer cell growth[1][5]. The combination aims to enhance pathway modulation and produce synergistic anti-tumor effects by vertically targeting the KRAS/MAPK cascade[6]. Both drugs are administered orally, and clinical trials are assessing their safety, tolerability, pharmacokinetics, and preliminary efficacy, predominantly in cancers with KRAS mutations such as non-small cell lung cancer, colorectal cancer, and other solid tumors[1][3][7].

Other names

SOS1::KRAS inhibitor + MEK inhibitorBI 1701963 combinationBI1701963 combinationBI-1701963 combination