470P - Comparative Pharmacokinetics of Trastuzumab Subcutaneous Formulation Administered Using a Proprietary Single-Use Injection Device, or Manually Using a Syringe

Abstract

ABSTRACT Background Intravenous (IV) trastuzumab, alone or with chemotherapy, is the standard of care for HER2-positive breast cancer and metastatic gastric cancer. The subcutaneous (SC) formulation of trastuzumab has shown non-inferiority vs. trastuzumab IV in a large Phase III study (Jackisch, et al. 2012). A proprietary single-use injection device (SID) has been developed to enable automated injection of trastuzumab SC formulation, thus offering potential for self-administration. In previous studies, trastuzumab SC was injected manually. Methods This randomized, open-label study assessed the pharmacokinetic (PK) comparability and safety of a single 600 mg dose of trastuzumab SC injected manually (N = 60) or using the SID (N = 59) in healthy male subjects. PK and safety were assessed before dosing and up to day 63 after dosing, with cardiac safety monitoring up to Week 21. Results The primary analysis showed that the study met the pre-specified criteria for comparability between modes of administration, as demonstrated by AUC0–21 days and Cmax values. Sensitivity analyses to assess possible variability due to body weight and actual dose delivered supported the co-primary analysis findings. The incidence of adverse events (AEs) of any grade was similar between arms with no grade 4 AEs, deaths, or cardiac, serious or SID-related AEs. Two grade 3 AEs occurred: pyrexia and head injury, both in the manual administration arm. Pain assessments and infusion-related/injection site reactions were similar. SID attachment and wearing comfort received top scores in all cases, while SID removal received the top score in all but two cases (acceptable). There were no SID failures. The incidence of antibodies to trastuzumab and recombinant human hyaluronidase was similar between arms, with no neutralizing antibodies detected and no relevant effects on PK observed. Conclusion This study demonstrated comparability of two modes of administration for trastuzumab SC based on standard PK parameters, with comparable safety for trastuzumab SC administered manually and using the single-use injection device, which demonstrated consistent performance and tolerability. Disclosure M. Lehle: Michaela Lehle is an employee of F. Hoffmann-La Roche Ltd. D. Heinzmann: Dominik Heinzmann is an employee of F. Hoffmann-La Roche Ltd and a stockholder in Roche Holdings. R. Mangat: Ranvir Mangat is an employee of Genentech Inc, and a stockholder of Roche Holdings. C. Li: Chunze Li is an employee of Genentech Inc, and a stockholder of Roche Holdings. L.A. Herraez-Baranda: Luis Herraez-Baranda is an employee of F. Hoffmann La-Roche Ltd. B.L. Lum: Bertram Lum is an employee of Genentech Inc, and a stockholder of Roche Holdings. All other authors have declared no conflicts of interest.