The effects of imatinib and food on the pharmacokinetics of asciminib

Asciminib, a first-in-class, Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor of BCR-ABL1 with the potential to overcome resistance to ATP-competitive tyrosine kinase inhibitors (TKIs), is being investigated in leukemias as monotherapy and in combination with TKIs including imatinib. This Phase 1 study in healthy volunteers assessed the effect of imatinib (steady-state; 400 mg once daily, with a low-fat meal) or food (to improve tolerability of imatinib) on the pharmacokinetics (PK) of asciminib (40 mg single dose; final market formulation). Asciminib + imatinib resulted in a 2-fold increase in asciminib exposure (area under the curve, AUC) and a 1.6-fold increase in asciminib Cmax compared with single-agent asciminib. The PK of imatinib was not substantially impacted by asciminib. Compared with fasted conditions, asciminib administered with food decreased asciminib AUC by 30-60%, depending on the meal’s fat content. Asciminib + imatinib was well tolerated with no new safety signals. Overall, co-administration of imatinib 400 mg once daily with asciminib 40 mg once daily under low-fat meal conditions resulted in increased asciminib exposure, similar to that provided with the recommended asciminib single-agent dose (40 mg twice daily) under fasted conditions. Single-agent asciminib should be administered in the fasted state to avoid suboptimal exposure.