A randomized, double-blind, three-arm, parallel group, phase 1 study to assess the pharmacokinetics, safety, and tolerability of PERT-IJS following a single dose of 420 mg intravenous infusion compared to the EU- and US-marketed drug product (pertuzumab; PERT) in healthy male volunteers.

e13009 Background: PERT-IJS is a proposed biosimilar to reference pertuzumab (PERT). This study assessed the pharmacokinetic (PK) equivalence, safety, tolerability, and immunogenicity of PERT-IJS compared with EU-approved PERT (EU-PERT) and US-licensed PERT (US-PERT) and EU-PERT versus US-PERT. Methods: In this double-blind, three-arm, parallel group, Phase 1 study, healthy male subjects were randomized 1:1:1 to 60±5 mins of a single 420 mg intravenous infusion of PERT-IJS (n = 50), EU-PERT (n = 50), or US-PERT (n = 49). Sentinel dosing with one subject from each treatment arm was performed initially to ensure optimal safety. PK, safety, and immunogenicity were evaluated for 91 days after dosing. The primary endpoint was area under the serum concentration–time curve (AUC) from time 0 to infinity (AUC 0-∞ ), and secondary endpoints were maximum serum concentration (C max ) and AUC from time 0 to the last measurable concentration at time t (AUC 0-t ) for pertuzumab. The pre-defined equivalence criterion was a 90% confidence interval (CI) of 80.00–125.00% for ratios of geometric least squares means (LSMs) among the test and reference products. Safety data were collected throughout the study and analyzed descriptively. Results: A total of 149 subjects, mean age 41.6 years, were randomized to the study treatments. The 90% CIs of the ratios of geometric LSMs were within the pre-defined bioequivalence interval of 80.00-125.00% for the primary and secondary endpoints (Table). Safety and tolerability profiles were also comparable among the treatment groups. The anti-drug antibody rates were comparable in all three treatment groups. Conclusions: This study demonstrated PK bioequivalence as well as comparable safety, tolerability, and immunogenicity between PERT-IJS versus EU-PERT/US-PERT and EU-PERT versus US-PERT in healthy male subjects. Clinical trial information: 2022-001691-34 . Statistical results of pertuzumab pharmacokinetics parameters. Treatment Comparison PK Parameter Geometric Least Squares Means Ratio 90% Confidence Interval PERT-IJS/EU-PERT AUC 0-∞ (mcg·h/mL) 0.97 91.48%-103.34% PERT-IJS/US-PERT AUC 0-∞ (mcg·h/mL) 0.94 88.25%-99.69% EU-PERT/US-PERT AUC 0-∞ (mcg·h/mL) 0.96 90.74%-102.55% PERT-IJS/EU-PERT AUC 0-t (mcg·h/mL) 0.97 91.39%-103.32% PERT-IJS/US-PERT AUC 0-t (mcg·h/mL) 0.94 88.06%-99.56% EU-PERT/US-PERT AUC 0-t (mcg·h/mL) 0.96 90.61%-102.47% PERT-IJS/EU-PERT C max (mcg/mL) 1.00 94.28%-106.01% PERT-IJS/US-PERT C max (mcg/mL) 0.97 91.70%-103.12% EU-PERT/US-PERT C max (mcg/mL) 0.97 91.71%-103.16%