Repotrectinib is approved in the US for treating ROS1-positive non-small cell lung cancer (NSCLC) and solid tumors harboring an NTRK gene fusion. A Population Pharmacokinetic (PopPK) model for repotrectinib was developed using data from 620 adults (118 healthy volunteers and 502 patients) across seven studies and 24 pediatric patients from one study. The PopPK model, a two-compartment model with first-order absorption and an absorption lag time, incorporating a time-varying clearance due to drug-induced autoinduction, adequately described all PK data. Clearance was modeled as a time- and concentration-dependent (Ctrough) autoinduction process, accounting for increased clearance over time. While empirical in nature, this Ctrough-driven autoinduction model effectively described the changes in clearance and avoided the abrupt concentration changes that can occur with discrete dose-driven autoinduction models. Additionally, this approach avoided time-consuming differential equation computations for the semi-mechanistic enzyme turnover autoinduction models. The model estimated that the maximum drug-induced clearance (CLMAX) was 4.9 times the baseline clearance. Body weight (BW) effects on clearance and volume of distribution were estimated as allometric scaling exponents of 0.477 and 0.962, respectively. Age was found to affect CLMAX, with younger patients generally exhibiting higher CLMAX values. Simulations suggested that a flat dosing regimen (e.g., 160 mg QD for 14 days followed by 160 mg BID) provides comparable drug exposures in both adult and adolescent patients. The PopPK model supported the health authority approval of the dosing regimen for repotrectinib in both adult and adolescent patients with NTRK gene fusion-positive solid tumors.