A phase I, randomized, double-blind, parallel, single-dose pharmacokinetic study to evaluate the biosimilarity of KM118 (proposed pertuzumab biosimilar) with reference pertuzumab (Perjeta®) in healthy male subjects

ObjectiveKM118 is a biosimilar to pertuzumab (Perjeta (R)). This study aimed to prove the pharmacokinetics (PK) biosimilarity and evaluate the safety, tolerability, and immunogenicity of KM118 and the original drug Perjeta (R) so that it can be approved for the marketing of biosimilar drugs in China.MethodsThis was a single-center, randomized, double-blind, two-arm, parallel-group, phase 1 study in healthy male subjects. The sample size was 100 cases. The dosage was 420 mg. Venous blood was collected from the beginning of drug administration to 84 days after drug administration, and the concentration of pertuzumab was determined using ELISA. The primary pharmacokinetic parameter was the area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) for pertuzumab. If the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of the primary parameters fell within the predefined range of 80.00-125.00%, biosimilarity was considered to be established. The safety and immunogenicity were evaluated.ResultsFifty subjects received 420 mg of intravenous injection of the test (KM118) formulation and 50 subjects received the reference (Perjeta (R)) pertuzumab formulation. The geometric mean of AUC0-t for the test formulation was 74465.82 +/- 16308.38 ng<middle dot>h/mL and for the reference formulation was 69097.83 +/- 13278.28 ng<middle dot>h/mL. The 90% confidence intervals (CIs) for the test/reference ratio for the AUC0-t of pertuzumab ranged from 99.92 to 114.72%, which met the bioequivalence criteria (80.00-125.00%). Similar immunogenicity was observed between Sequences A and B. All of the adverse events (AEs) were Grade 1 or 2, and no SAEs occurred. The test and reference formulations of pertuzumab were well-tolerated by healthy male subjects.ConclusionBiosimilarity between the test and reference formulations of pertuzumab (KM118 and Perjeta (R)) was demonstrated. Both formulations were well tolerated.Clinical Trial RegistrationchinaDrugtrials.org.cn, identifier CTR20202566 (December 17, 2020); chictr.org.cn, identifier ChiCTR2400092982 (November 26, 2024).