Model-Based Alternative Dosing Strategies for Subcutaneous Nivolumab to Improve Cost Effectiveness

Area of Science:

• Pharmacology and Oncology
• Drug Development and Administration

Background:

• Subcutaneous nivolumab (SC nivolumab) use presents financial, environmental, and capacity challenges.
• Current fixed SC dosing shows higher exposure and variation than historical intravenous dosing.

Purpose of the Study:

• To develop alternative SC nivolumab dosing regimens.
• Aim to reduce drug expenses and patient treatment burden.
• Ensure effective drug exposure with new regimens.

Main Methods:

• Population pharmacokinetic simulations used.
• Alternative SC regimens explored via a pharmacokinetic model.
• Patients stratified by weight (<60 kg, 60-90 kg, >90 kg).
• Two experimental progressive regimens developed: concentration-driven and IV infusion of SC formulation.

Main Results:

• A bodyweight-based regimen (1200 mg every 5-7 weeks) saves 35% annually.
• An extended-interval regimen (1200 mg every 10 weeks) saves 60% annually, maintaining 2.5 mg/L trough concentration.
• IV infusion of SC formulation every 7 weeks saves 43% annually.

Conclusions:

• Bodyweight-dependent interval dosing is cost-effective, patient-friendly, and optimizes SC nivolumab use.
• Proposed regimens support clinical non-inferiority studies comparing alternative to standard dosing.