Study of the pharmacokinetics, pharmacodynamics, and safety of the biosimilar pembrolizumab RPH-075 compared to Keytruda® in patients with malignant neoplasms

Introduction: Pembrolizumab is a humanized monoclonal antibody selectively blocking the interaction between the PD-1 receptor and its ligands. The drug RPH-075 is a biosimilar to the original Keytruda®.Objective: To establish the equivalence of pharmacokinetic (PK) properties, as well as pharmacodynamic (PD) parameters, safety, and immunogenicity of the drug RPH-075 compared to Keytruda® in patients with malignant tumors.Materials and Methods: This multicenter double-blind randomized study included 90 patients with melanoma and non-small cell lung cancer who were randomized into two treatment groups (RPH-075 and Keytruda ®) in 1:1 ratio. In both groups, pembrolizumab was administered as monotherapy at a dose of 200 mg intravenously every 3 weeks until progression or intolerable toxicity. The primary aim of the study was to assess PK after the first administration. The primary endpoint for PK assessment was AUC(0-504), and for safety, it was the frequency of adverse events (AE). The decision on PK equivalence was planned to be made if the two-sided 90 % confidence interval (CI) for the geometric mean ratio of AUC(0-504) after a single administration of each drug would be within 80.00-125.00 %. Secondary endpoints included Cmax after the first administration, as well as the other PK, safety, and immunogenicity parameters. This study also assessed PK and PD parameters after multiple administrations, and a pilot efficacy assessment was planned.Results: This article presents the analysis of data from the first stage of the study (after the first drug administration with a 3-week observation period). The data analysis was blinded, and the treatment groups were coded as A and B. The 90 % CI for the geometric mean ratio of AUC(0-504) after the administration of drug A to AUC(0-504) of drug B was 93.50-121.16 %, and for the ratio of B to A, it was 82.54-106.95 %. The obtained intervals met the specified equivalence limit of 80.00-125.00 %, allowing us to conclude that RPH-075 and original Keytruda® are PK equivalent. Both drugs demonstrated comparably high saturation of PD-1 receptors on CD4+ / CD8+ lymphocytes at the end of the first cycle (day 22). Binding antibodies to pembrolizumab were detected in 2 patients (one in each group) over the analyzed period, indicating comparably low immunogenicity for both drugs. Safety profile analysis during this period revealed 7 AEs in 4 patients in group A and 4 AEs in 3 patients in group B. The frequency of AEs did not significantly differ between the groups.Conclusions: PK, PD, immunogenicity, and safety parameters of the pembrolizumab biosimilar RPH-075 were equivalent to those of the original Keytruda®.