Aim <p>Enfortumab vedotin is an antibody-drug conjugate (ADC) that has been approved for locally advanced or metastatic urothelial cancer, as monotherapy and in combination with pembrolizumab, and has shown significant benefit in progression-free survival and overall survival for these patients. The economic burden of enfortumab vedotin hampers widespread patient access. The aim of this study was to develop a model-informed alternative dosing regimen that results in equivalent drug exposure while reducing the costs and prevent drug spillage.</p> Methods <p>Population pharmacokinetic modelling was used to simulate a dosing regimen leading to equivalent exposure by using the published population pharmacokinetic model in the registration reports. The alternative dosing regimen was based on weight-bands derived from the established non-linear relationship between body weight and systemic exposure, and the usage of whole vials based on fixed doses to prevent spillage. Equivalent exposure compared to the approved body weight-based dosing regimen was defined as conservative equivalent boundaries of 90–111% for the calculated geometric mean ratios (GMRs) of area under the concentration-time curve and trough concentration.</p> Results <p>A weight-band based dosing regimen for each dose level of enfortumab vedotin was developed. The GMRs for all pharmacokinetic outcomes were within the predefined equivalence boundaries. In addition, a more even exposure distribution was observed across the body weight quartiles. The average costs savings across all dose levels and per weight-band were approximately 15%.</p> Conclusion <p>The proposed alternative dosing regimen shows that drug costs and spillage of enfortumab vedotin can be reduced while maintaining an equivalent and more evenly distributed exposure in treated patients.</p>