sotorasib + TNO155

**sotorasib + TNO155** is an investigational combination of two oral small-molecule inhibitors developed for the treatment of cancers driven by KRAS G12C mutations. **Sotorasib** is a selective covalent inhibitor of the KRAS G12C oncoprotein, leading to impaired downstream MAPK signaling, cell cycle arrest, and apoptosis. **TNO155** is a potent allosteric inhibitor of SHP2 (PTPN11), a key upstream regulator of RAS/MAPK signaling. The combination is designed to overcome acquired resistance and enhance the antitumor effect of each monotherapy by simultaneously inhibiting both KRAS G12C (with sotorasib) and SHP2 (with TNO155), which may prevent reactivation of the RAS pathway from upstream compensatory signals. Preclinical studies suggest sotorasib + TNO155 may produce greater reduction in ERK phosphorylation and Ras-GTP compared to monotherapy, supporting potential synergistic efficacy, particularly in KRAS G12C-mutant solid tumors such as non–small cell lung cancer and colorectal cancer[1][3].

Other names

sotorasib + TNO155