Adagrasib (MRTX849)

To evaluate the breadth of MRTX849 activity, its effect on cell viability is determined across a panel of 17 KRAS^G12C-mutant and three non-KRAS^G12C-mutant cancer cell lines using 2D (3-day, adherent cells) and 3D (12-day, spheroids) cell growth conditions. MRTX849 potently inhibits cell growth in the vast majority of KRAS^G12C-mutant cell lines with IC50 values ranging between 10 nM and 973 nM in the 2D format and between 0.2 nM and 1042 nM in the 3D format.^[1].

All cell lines were maintained at 37 ℃ in a humidified incubator at 5% CO2 and were periodically checked for mycoplasma. CellTiter-Glo assay to evaluate cell viability performed on seven KRAS G12C-mutant cell lines and three non-KRAS G12C-mutant cell lines cells grown in 2D tissue culture conditions in a 3-day assay or 3D conditions using 96-well, ULA plates in a 12-day assay.

Rapid tumor regression is observed at the earliest posttreatment tumor measurement and animals in the 30 mg/kg and 100 mg/kg cohorts exhibits evidence of a complete response at study Day 15. Dosing is stopped at study Day 16 and all 4 mice in the 100 mg/kg cohort and 2 out of 7 mice in the 30 mg/kg cohort remains tumor-free through study Day 70.^[1].