Taste Profile and Relative Bioavailability of Tovorafenib Powder for Oral Suspension and Food Effect of the Tovorafenib Tablet in Healthy Participants

Abstract

A pediatric-friendly powder for oral suspension (PfOS) of tovorafenib, a type II RAF inhibitor, was developed for patients with difficulty swallowing tablets. This open-label, randomized, phase 1 study (QSC205140) evaluated the taste/palatability of PfOS formulations (n = 12), the relative bioavailability of the PfOS versus tablet formulation, and the food effect on tablets (n = 12) in healthy participants. Tovorafenib was initially administered at 300 mg and reduced to 100 mg due to musculoskeletal adverse events (AEs). The addition of sweetener and/or flavoring improved taste/palatability. Geometric mean ratios (90% confidence interval) of dose-corrected peak plasma drug concentration (C_max/D) and area under the plasma concentration–time curve from time zero to the last measurable concentration (AUC_0-last/D) between the PfOS and tablet formulations were 96% (83%-111%) and 104% (95%-115%), respectively. Compared with fasted administration, administration of the tablet with food resulted in a 2-3.5-hours delay in time to C_max, and a 20% reduction in C_max/D with no change in AUC_0-last/D. Four severe and 7 moderate AEs occurred with 300 mg of tovorafenib. All remaining AEs, reported with both 100 mg and 300 mg, were mild. These data suggest that tovorafenib PfOS and tablet formulations are comparable, and that the tablet can be administered with or without food.