Pharmacokinetics, Safety, and Immunogenicity of a Biosimilar of Nivolumab (LY01015): A Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Trial in Healthy Chinese Male Subjects

Background

Nivolumab (Opdivo^®) is the first anti-PD-1 antibody approved in the world. LY01015 is a potential biosimilar of nivolumab.

Objectives

This phase I study aimed to establish the pharmacokinetic equivalence between LY01015 and the original investigational nivolumab (Opdivo^®) in healthy Chinese male subjects. Additionally, safety and immunogenicity were assessed.

Patients and Methods

A randomized, double-blind, parallel-controlled, phase I trial was conducted with 176 healthy male adults receiving a single intravenous infusion of LY01015 or nivolumab at 0.3 mg/kg. Pharmacokinetics, safety, and immunogenicity were evaluated over a 99-day period. The primary pharmacokinetics endpoint was AUC_0–∞, and the secondary pharmacokinetic endpoints included AUC_0–t and C_max. Pharmacokinetic bioequivalence was confirmed using standard equivalence margins of 80.00–125.00%.

Results

This study is the first to report on the pharmacokinetics, safety, and immunogenicity of Opdivo^® in healthy individuals. The pharmacokinetics profiles of LY01015 and Opdivo^® were found to be comparable. The geometric mean ratios (90% confidence intervals) for the AUC_0–∞, AUC_0–t, and C_max of LY01015 to Opdivo^® were 94.49% (90.29–98.88%), 94.92% (88.73–101.54%), and 96.55% (93.32–99.90%), respectively, falling within the conventional bioequivalence criteria of 80.00–125.00%. The safety and immunogenicity were also comparable between the two groups.

Conclusions

LY01015 demonstrated highly similar pharmacokinetics to nivolumab in healthy Chinese male subjects. Both drugs exhibited comparable safety and immunogenicity profiles.

Trial Registration

This trial is registered at the Chinese Clinical Trial Registry website (https://www.chictr.org.cn/#ChiCTR2200064771).