Pharmacokinetic bioequivalence of the fixed-dose combination of pertuzumab and trastuzumab administered subcutaneously using a handheld syringe or an on-body delivery system.

Abstract

Purpose: This randomized, open-label, two-arm, parallel-group, single dose, multi-center phase I study (ClinicalTrials.gov ID, NCT05275010) investigated the comparability of the pharmacokinetics of a new formulation combining pertuzumab (P) and trastuzumab (H) in one fixed-dose combination for subcutaneous injection (FDC SC) using a proprietary on-body injector (OBI) or a handheld syringe with hypodermic needle in healthy male subjects.

Methods: Healthy male subjects were randomized 1:1 to either PH FDC SC using a handheld syringe (Arm 1) or an OBI device (Arm 2). Co-primary endpoints were: (i) area under the time-concentration curve (AUC) from the start of dosing to day 63 (AUC_0-62) of serum P, (ii) maximum serum concentration (C_max) from start of dosing to 63 days of serum P, (iii) AUC from the start of dosing to day 63 (AUC_0-62) of serum H, and (iv) C_max from start of dosing to 63 days of serum H. Safety was a key secondary endpoint. Liquid chromatography coupled to tandem mass spectrometry was used to measure pertuzumab and trastuzumab simultaneously in serum samples.

Results: The obtained geometric mean ratios for C_max and AUC_0-62 were within the pre-specified bioequivalence margins (0.80, 1.25) for both P and H, therefore meeting the criteria for bioequivalence. No discontinuations due to safety reasons were reported. Overall, the final safety analysis with longer follow-up was consistent with the primary analysis; there were no new or unexpected safety findings.

Conclusion: This study demonstrated the feasibility of a hands-free device approach to deliver pertuzumab and trastuzumab in one fixed-dose combination for subcutaneous injection without compromising pharmacokinetics and safety.