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

Abstract

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).