Population Pharmacokinetic and Pharmacodynamic Analysis of Navtemadlin in Patients with Relapsed and Refractory (R/R) Myelofibrosis (MF) and Other Myeloid or Solid Tumor Malignancies

This study conducted a population pharmacokinetic (PK) and pharmacodynamic (PD) analysis of navtemadlin, an MDM2 inhibitor, across multiple cancer types, including relapsed and refractory (R/R) myelofibrosis (MF), Merkel cell carcinoma (MCC), and other malignancies. Using a PK model based on 318 subjects, researchers found that tumor type influenced navtemadlin’s absorption, clearance, and exposure, with factors like inflammation, age, and sex also impacting drug levels. The PD marker MIC-1 increased in a concentration-dependent manner, though baseline levels varied by cancer type. These findings support navtemadlin’s dose selection for Phase 3 trials in MF and highlight its potential for p53-driven anti-tumor activity.