LAUSR

Background: Xeris Pharmaceuticals (Chicago, IL, USA) has developed the proprietary XeriJect® technology, which uses a novel viscoelastic suspension for delivery of high-concentration, low-volume subcutaneous (SC) injections of therapeutic antibodies. Trastuzumab (TmAb) is a monoclonal antibody that selectively binds and inhibits human epidermal growth factor receptor 2 protein (HER2). It is widely used for the treatment of certain types of breast, stomach, and esophageal cancer, and is commercially available for both intravenous (IV) infusion (Herceptin®, Genentech Inc., South San Francisco, CA, USA) [Herceptin IV] and SC injection (Herceptin Hylecta®, Genentech Inc., South San Francisco, CA, USA) [Hylecta SC]. XeriJect TmAb is a stable formulation of a trastuzumab biosimilar at a higher concentration (432 mg/mL) than Hylecta (120 mg/mL) for SC administration, thus enabling lower injection volumes. This study evaluated and compared XeriJect TmAb SC (120 mg) to Herceptin IV (10 mg/kg) and Hylecta SC (120 mg) in a minipig pharmacokinetic model. Results: Among a total of 12 minipigs, Herceptin was administered IV at 10 mg/kg over a 90-minute infusion and all other formulations were administered at a target dose of 120 mg SC. Due to the higher concentration of XeriJect TmAb, the injection volume of Xeriject TmAb (0.28 mL) was considerably lower than Hylecta (1 mL). XeriJect TmAb was rapidly absorbed similar to Hylecta after SC administration with a median Tmax of 1.0 days with both formulations and a mean Cmax/Dose of 9.7 and 9.5 kg*µg/mL/mg, respectively. In contrast, Herceptin IV produced a median Tmax of 0.06 days and Cmax/Dose of 18.0 kg*µg/mL/mg. All formulations (Herceptin IV, Hylecta SC, XeriJect TmAb SC) demonstrated similar elimination profiles and exposure as assessed by AUClast/Dose. The mean [SD] AUClast/Dose of XeriJect TmAb (108 [4.2] day*kg*µg/mL/mg) was similar to Hylecta SC (109 [22.4] day*kg*µg/mL/mg) and Herceptin IV (97 [7.5] day*kg*µg/mL/mg). The mean [SD] elimination half-life of XeriJect® TmAb SC (11.4 [10.1] days) was also similar to Hylecta® SC (11.3 [4.8] days) and longer than with Herceptin® IV (8.8 [2.1] days). Conclusion: We have demonstrated for the first time that administration of XeriJect TmAb, a stable high-concentration formulation of trastuzumab administered SC, produced rapid absorption and similar pharmacokinetics to commercially available Herceptin IV and Hylecta SC in a preclinical pharmacokinetic model. Citation Format: Rick Fitch, Diana Bowman, Martin Donovan, Steven Prestrelski. Pharmacokinetics of a novel viscoelastic suspension of trastuzumab biosimilar for high-concentration, low-volume subcutaneous injection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB024.