Whole blood stability evaluation of monoclonal antibody therapeutics using volumetric absorptive microsampling.

Volumetric absorptive microsampling (VAMS) is increasingly utilized for both nonclinical and clinical pharmacokinetic studies. Currently, VAMS is employed as the sampling method for the detection of antibodies for coronavirus disease 2019. Biotherapeutics whole blood stability on VAMS presents as a critical concern for the health and pharmaceutical industries. In this follow-up to our previous publication, we evaluated daclizumab and trastuzumab whole blood sample stability on VAMS. The drug recovery data we observed at room temperature for short term and -80°C for long term was very encouraging. The knowledge could help us better understand and plan important investigation timelines, especially pandemic situations where human whole blood samples from a large population are collected and in urgent need of data analysis.

Impact of Dose Delays and Alternative Dosing Regimens on Pertuzumab Pharmacokinetics.

PERJETA (pertuzumab), administered with Herceptin (trastuzumab), is used in the treatment of human epidermal growth factor receptor 2-positive breast cancer. Pertuzumab is currently approved with an initial loading dose of 840 mg, followed by a 420-mg maintenance dose intravenously every 3 weeks. A reloading dose is required if there is a ≥6-week delay in treatment. In response to the potential treatment disruption due to COVID-19, the impact of dose delays and alternative dosing regimens on intravenous pertuzumab for human epidermal growth factor receptor 2-positive breast cancer treatment is presented. Simulations were conducted by using the validated population pharmacokinetic model for pertuzumab, and included (1) 4-, 6-, and 9-week dose delays of the 840 mg/420 mg every 3 weeks dosing regimen and (2) 840 mg/420 mg every 4 weeks and 840 mg every 6 weeks alternative dosing regimens. Simulations were compared with the currently approved pertuzumab dosing regimen. The simulations in 1000 virtual patients showed that a dose reload (840 mg) is required following a dose delay of ≥6 weeks to maintain comparable Ctrough (lowest concentration before the next dose is given) levels to clinical trials. The 840 mg/420 mg every 4 weeks and 840 mg every 6 weeks alternative dosing regimens decrease median steady-state Ctrough by ≈40% compared with the approved regimen, and <90% of patients will be above the target Ctrough . Thus, the alternative 840 mg/420 mg every 4 weeks and 840 mg every 6 weeks pertuzumab dosing regimens are not recommended. Flexibility for intravenous PERJETA-based regimens is available with an alternative route of pertuzumab administration (subcutaneous vs intravenous).