adagrasib + TNO155

**Adagrasib + TNO155** is an investigational combination therapy comprising adagrasib, a covalent inhibitor selective for the mutant KRAS G12C, and TNO155, an oral, allosteric inhibitor of SHP2 (PTPN11). Adagrasib irreversibly binds the GDP-bound inactive form of KRAS G12C, preventing its activation and downstream signaling via the MAPK pathway. Resistance to KRAS G12C inhibition can develop through SHP2-mediated feedback and receptor tyrosine kinase (RTK) signaling. TNO155 inhibits SHP2, thereby blocking upstream signaling that activates RAS proteins, including KRAS, and modulating the ERK pathway. Preclinical and early clinical data indicate that the combination enhances antitumor activity versus either monotherapy, with increased tumor regression and suppression of downstream growth and survival pathways. This combination is under investigation for advanced solid tumors, particularly those harboring KRAS G12C mutations[1][2][5][7].

Other names

adagrasib + TNO155