Immunogenicity of Atezolizumab: Influence of Testing Method and Sampling Frequency on Reported Anti-drug Antibody Incidence Rates.

Measurement of anti-drug antibodies (ADA) to assess the incidence of ADA in a clinical trial is a critical step in immunogenicity assessment during the development of a protein therapeutic. We developed novel graphical approaches to illustrate clinical trial ADA data for the PD-L1 inhibitor atezolizumab (Tecentriq) that included a systematic analysis of the impact of the timing of ADA sampling and ADA assay drug tolerance on reported ADA incidence. We found that approaches used across the industry for ADA incidence analysis provide a limited view of immunogenicity in oncology studies, where ADA detection may be confounded by both drug dosage and patient attrition.

Brief Report: Updated Data From IMscin001 Part 2, a Randomized Phase III Study of Subcutaneous Versus Intravenous Atezolizumab in Patients With Locally Advanced or Metastatic NSCLC.

Introduction: Subcutaneous atezolizumab is approved for the treatment of various solid tumors. Previous results from the IMscin001 study (NCT03735121) revealed that the pharmacokinetics, efficacy, immunogenicity, and safety of subcutaneous and intravenous atezolizumab were consistent (data cutoff: April 26, 2022). We present updated data from this trial (data cutoff: January 16, 2023).

Early Clinical Development of Lufotrelvir as a Potential Therapy for COVID-19.

Lufotrelvir was designed as a first in class 3CL protease inhibitor to treat COVID-19. Development of lufotrelvir was challenged by its relatively poor stability due to its propensity to epimerize and degrade. Key elements of process development included improvement of the supply routes to the indole and lactam fragments, a Claisen addition to homologate the lactam, and a subsequent phosphorylation reaction to prepare the prodrug as well as identification of a DMSO solvated form of lufotrelvir to enable long-term storage.

IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications.

Background: Atezolizumab intravenous (IV) is approved for the treatment of various solid tumours. To improve treatment convenience and health care efficiencies, a coformulation of atezolizumab and recombinant human hyaluronidase PH20 was developed for subcutaneous (SC) use. Part 2 of IMscin001 (NCT03735121) was a randomised phase III, open-label, multicentre, noninferiority study comparing the drug exposure of atezolizumab SC with atezolizumab IV.