The pharmacokinetics (PK) of intravenous (IV) nivolumab is well characterized. A subcutaneous (SC) nivolumab formulation with and without recombinant human hyaluronidase PH20 enzyme is being evaluated in CheckMate 8KX (NCT03656718). A model-based analysis was conducted to characterize the PK of nivolumab SC and predict systemic exposures after IV and SC administration to guide dosing regimen selection for nivolumab SC. A prior IV model was modified to incorporate an SC extravascular compartment and estimate the absorption rate constant (K a ) and bioavailability (F) of nivolumab SC. Serum concentration-time data from 82 patients treated with nivolumab SC 720, 960, or 1200 mg were pooled with existing IV data from multiple studies for model development. Prediction-corrected visual predictive check (pcVPC) plots assessed the model's performance. Stochastic simulations were conducted to predict exposures for IV and SC administration. The data were described by a two-compartment model with time-varying clearance, zero-order infusion into the central compartment after IV dosing, and first-order absorption from the extravascular compartment after SC dosing. The pcVPC suggested that the model adequately described the observed nivolumab SC data. Predicted nivolumab exposures at 1200 mg SC every 4 weeks (Q4W) were higher than those at the approved dose of 3mg/kg IV Q2W and lower than those at the highest tested safe dose of 10mg/kg IV Q2W. Nivolumab PK is well characterized using the combined SC/IV population PK model. The model-based analysis facilitated a comprehensive benefit-risk assessment of nivolumab SC and informed selection of 1200 mg SC Q4W for phase III evaluation.