Flat dose regimen of toripalimab based on model-informed drug development approach

Area of Science:

• Pharmacology
• Immunotherapy
• Clinical Trials

Background:

• Flat dosing regimens are increasingly approved for programmed death receptor-1 (PD-1) inhibitors, including toripalimab.
• Current toripalimab dosing is 3 mg/kg every 2 weeks (Q2W).
• Evaluating a 240 mg Q3W flat dose is crucial for pharmacological evidence.

Purpose of the Study:

• To provide pharmacological evidence supporting a flat dosing regimen for toripalimab.
• To assess the efficacy and safety of a 240 mg Q3W flat dose compared to 3 mg/kg Q2W.
• To establish a preferred therapeutic dosage for toripalimab.

Main Methods:

• A population pharmacokinetic (PopPK) model was developed using data from 1,014 patients across 13 clinical studies.
• Exposure-response (E-R) and exposure-safety analyses were conducted using logistic regression and Cox proportional hazard models.
• Key endpoints included objective response rate (ORR), adverse events (AEs), and progression-free survival (PFS).

Main Results:

• The 240 mg Q3W flat dose demonstrated comparable pharmacokinetic profiles and steady-state exposures to the 3 mg/kg Q2W regimen.
• No increased probability of adverse events was observed with higher toripalimab exposure.
• A flat exposure-response relationship for ORR and exposure as a predictor for PFS were identified, with no significant difference in treatment benefit across exposure quantiles.

Conclusions:

• The 240 mg Q3W flat dosing regimen for toripalimab is pharmacologically supported.
• This regimen exhibits comparable efficacy and safety to the current 3 mg/kg Q2W dose.
• The 240 mg Q3W flat dose is recommended as a preferred, more convenient therapeutic option for toripalimab.