A Potential Best-in-Class KRASG12C Inhibitor? The Science Behind How Adagrasib Differentiates from Sotorasib

Mirati’s “Breakthrough” KRASG12C inhibitor, adagrasib, was granted accelerated approval by the FDA in 2022. As it follows Amgen’s first-in-class KRASG12C inhibitor, sotorasib, adagrasib is constantly scrutinized for any evidence it may be different, or better, than sotorasib. This deep dive reviews the current understanding on how adagrasib differs from sotorasib and why, including:

• Is adagrasib really CNS-penetrant?

• What properties would make adagrasib more CNS-penetrant than sotorasib?

• Why does adagrasib appear to be less hepatotoxic with immunotherapy?

• How was adagrasib discovered? and more…