3.5 Metabolite (M12) PK Exposure Relative to Parent (iberdomide)
Based on the model, AUC and Cmax for each individual patient who had both iberdomide and M12 PK data (Cohorts A, B and E from MM-001 study) were simulated. Metabolite to parent ratio was calculated and stratified by dose and cohort (Figure 7 and Table 5). The goal was to assess the influence of dose and combination on the extent of metabolite exposure. Results showed that the metabolite to parent ratio (both in terms of Cmax and AUC) was consistent, irrespective of dose and cohorts. In addition, iberdomide and M12 PK profile were simulated for a typical MM patient on 1.6 mg 21/28 schedule and were overlaid in Figure 8. The plot showed that M12 PK profile generally tracked the PK of iberdomide, as demonstrated by the two parallel curves.
In conclusion, the totality of data suggested that iberdomide PK was adequate to represent the pharmacological active exposures in systemic circulation, regardless of time, dose and combinations.