PII-047 - AN OPEN-LABEL BIOEQUIVALENCE STUDY IN HEALTHY VOLUNTEERS TO COMPARE THE PHARMACOKINETICS OF TWO DIFFERENT TABLET STRENGTHS OF SOTORASIB IN THE FED AND FASTED STATE

P. Cardona¹, C. Sampson², J. Purkis³, B. Houk⁴; ¹Amgen, Inc, ²Amgen, , United States, ³Amgen, ⁴Clinical Pharmacology Modeling and Simulation, Amgen.

Background: Sotorasib is a small molecule KRASG12C inhibitor is indicated for the treatment of KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer. The approved dose is 960 mg once daily taken as 8 x 120 mg tablets. This study evaluated bioequivalence of a single high drug load tablet at a dose of 240 mg. The formulations evaluated were 1 x 240 mg tablets (fasted and fed) and 2 x 120 mg tablets (fasted).

Methods: This Phase 1, 3-period cross-over study enrolled 146 healthy subjects and 144 subjects completed the study. Subjects who completed the study received 240 mg sotorasib administered as 2 x 120 mg tablets and 1 x 240 mg tablets under fasted conditions. The subjects were randomized into treatment sequences AB or BA. 14 subjects proceeded to the food effect arm of the study. Blood samples were collected predose and up to 48 hours post dose. Plasma concentrations were measured using a validated high-performance liquid chromatography tandem mass spectrometry method. PK parameters were estimated using non-compartmental methods and summarized to test for bioequivalence. Safety and tolerability were monitored throughout the study.

Results: The geometric least squares means (GLSMs) ratios and 90% confidence interval administered as 1 x 240 mg tablets (test) and 2 x 120 mg tablets (reference) were 0.967 (0.908, 1.029) and 0.962 (0.880, 1.053) for AUCinf, and Cmax, respectively. The GLSMs ratios following 1 x 240 mg administration under fed conditions (high-fat meal) (test) were 1.440 (1.016, 2.041) and 1.337 (0.840, 2.128) for AUCinf, and Cmax, respectively, compared to fasted conditions (reference).
Sotorasib at 240 mg, administered as 1 x 240 mg tablet in the fasted and fed states, was generally safe and well tolerated by the majority of healthy subjects in this study.

Conclusion: A high drug load tablet formulation of sotorasib (240 mg) displayed bioequivalence to the approved formulation. The impact of food was consistent with the approved formulation, supporting that the high drug load tablet can be administered in fed and fasted state.