PII-092 - A PHASE 1 SINGLE ASCENDING DOSE (SAD) STUDY OF FOOD EFFECTS AND DRUG-DRUG INTERACTION (DDI) EFFECTS OF PH-MODIFYING AGENTS ON INCB099318 PHARMACOKINETICS (PK), A PROGRAMMED DEATH-LIGAND 1 (PD-L1) INHIBITOR, IN HEALTHY PARTICIPANTS

X. Gong, Z. Xun, C. Leonetti-Whalen, P. Wang, X. Chen, N. Punwani; Incyte Research Institute.

Background: We conducted a SAD study to evaluate food effects and DDI effects of pH-modifying agents on INCB099318 PK, and to assess the safety and tolerability of INCB099318 (PD-L1 inhibitor) tablets in healthy participants.

Methods: In the SAD study, 9 adult participants received a single oral dose of INCB099318 (20, 40, or 80 mg) and 3 participants in cohorts 1 and 2, and 2 participants in cohort 3, received placebo. The effect of a medium-fat meal was assessed using a 2-way crossover design; 12 participants received a single dose of INCB099318 (80 mg) with and without food. DDI effects of pH-modifying agents were assessed using a fixed-sequence design, in which 12 and 13 participants, respectively, received a single dose of INCB099318 80 mg with and without either famotidine (histamine type 2 [H2] antagonist) or esomeprazole (PPI). PK samples were collected serially predose and up to 96 hours postdose. PK parameters were derived by noncompartmental analysis.

Results: INCB099318 was rapidly absorbed in the fasted state, with a median tmax of 1 hour. Plasma concentrations then declined in a multiphasic manner, with a mean terminal t½ of ~3-6 hours. Single-dose plasma exposures of INCB099318 increased dose proportionally over the entire dose range studied (20 to 80 mg). Interindividual variability of INCB099318 plasma Cmax and AUC∞ was generally moderate. Administration of INCB099318 after a medium-fat meal significantly increased median tmax by 3 hours (P=0.0015) and decreased Cmax and AUC∞ by 58% and 40%, respectively. Administration of INCB099318 with famotidine did not impact INCB099318 exposure. Esomeprazole decreased Cmax and AUC∞ by 27% and 22%, respectively; however, this decrease in plasma INCB099318 exposure is not considered clinically relevant. All treatment-emergent AEs were mild or moderate, with no observed dose- or treatment-related trends. No serious adverse events (AEs) were reported.

Conclusion: INCB099318 PK was impacted by food. INCB099318 can be dosed concomitantly with pH-modifying H2 antagonists or PPIs. Single doses of INCB099318 were generally well tolerated in healthy participants. The exposure and safety results reported in this study support further clinical investigation of INCB099318.