SOS1 and neoplasm: BI-3406 dampens the key interaction between Tyr884SOS1-Arg73RAS for RAS activation, exhibits improved potency in KRAS-driven tumors both in vitro and in vivo, and synergizes with MEK inhibitor trametinib, resulting in remarkable tumor regressions with adequate tolerance.397,398 BI 1701963, the analog of BI-3406, is the only SOS1 inhibitor that has moved forward into clinical study.