OA03.03 Sotorasib in Combination with RMC-4630, a SHP2 Inhibitor, in KRAS p.G12C-Mutated NSCLC and Other Solid Tumors

Sotorasib, a specific and irreversible KRASG12C inhibitor, has demonstrated clinical activity as monotherapy in KRAS p.G12C-mutated solid tumors. Genomic alterations of receptor tyrosine kinase (RTK) were identified as a common putative resistance mechanism to sotorasib in the CodeBreaK100 Ph1/2 trial, highlighting the potential role for combining sotorasib with upstream RTK signaling inhibitors. In mouse xenograft models, combining sotorasib with a SHP2 inhibitor (SHP2i) impaired RTK signaling to RAS and enhanced anti-tumor efficacy.