Senior Scientist Amgen Inc. Thousand Oaks, California, United States
Background: Sotorasib is a small molecule KRASG12C inhibitor indicated for the treatment of KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer. It is approved to be taken as 960 mg orally once daily (8 x 120 mg tablets). This study evaluated the pharmacokinetics (PK) of 960 mg sotorasib administered as 3 x 320 mg tablets (fasted and fed) and 960 mg sotorasib administered as 8 x 120 mg tablets (fasted). Methods: This 3-period cross-over study enrolled 145 healthy subjects. Sotorasib 960 mg was administered as 8 x 120 mg tablets and 3 x 320 mg tablets under fasted conditions separated by washout. Thirteen out of 145 subjects also received 3 x 320 mg tablets with a high-fat meal. Blood samples were collected predose and up to 48 hours post dose. Plasma concentrations were measured using a validated method. PK parameters were estimated using non-compartmental methods. Safety was monitored throughout the study. Results: The geometric least squares means (GLSMs) ratios and 90% confidence intervals for sotorasib administered as 3 x 320 mg tablets (test) and 8 x 120 mg tablets (reference) under fasted conditions were 1.020 (0.977, 1.065) and 1.009 (0.980, 1.040) for AUCinf and Cmax, respectively. The GLSMs ratios for sotorasib (3 x 320 mg tablets) administered with a high-fat meal (test) compared to sotorasib (3 x 320 mg tablets) administered under fasted conditions (reference) were 1.484 and 1.001 for AUCinf and Cmax, respectively. There were no new safety signals for sotorasib. Conclusion: Sotorasib 960 mg administered as 3 x 320 mg tablets or 8 x 120 mg tablets were bioequivalent, suggesting that 3 x 320 mg tablets can serve to reduce pill burden. The effect of food with 3 x 320 mg tablets was consistent with the effect observed with 8 x 120 mg tablets in other studies. Sotorasib at 960 mg was safe and well tolerated in healthy subjects.
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