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Purpose <p>Atezolizumab is a monoclonal antibody against programmed cell death ligand 1 (PD-L1) used in oncology. With the intravenous formulation, the standard dose exceeds the established minimum effective concentration (MEC, 6&#xa0;μg/mL). A subcutaneous (SC) triweekly formulation was recently introduced. This study aimed to predict SC atezolizumab exposure under extended dosing regimens using a population pharmacokinetic (PopPK) model.</p> Methods <p>This study used a PopPK in silico model based on data from the IMscin001 trial (SC atezolizumab in non-small cell lung cancer) to predict exposure for SC atezolizumab 1875&#xa0;mg administered every 4, 5, 6, and 7&#xa0;weeks (q4w–q7w). Simulations were performed in Monolix. Minimum concentrations after the first cycle (C<sub>MIN,1</sub>) and at steady state (C<sub>MIN,SS</sub>) were assessed in 1000 simulations per interval, with efficacy defined by 99% of simulations maintaining trough concentrations above the 6&#xa0;μg/mL MEC.</p> Results <p>The model showed good agreement between simulated and observed plasma concentrations (PC), supporting its predictive performance. With q4w, C<sub>MIN,1</sub> was 29.48&#xa0;µg/mL and C<sub>MIN,SS</sub> was 34.42&#xa0;µg/mL, both well above the MEC. Similar results were found for q5w (C<sub>MIN,1</sub> at 18.13&#xa0;µg/mL; C<sub>MIN,SS</sub> at 22.85&#xa0;µg/mL). With q6w, PC remained above but close to the MEC, whereas q7w fell below this threshold.</p> Conclusions <p>Our PopPK model suggests that extending SC atezolizumab dosing to 4 or 5&#xa0;weeks maintains therapeutic efficacy and could serve as a clinically viable alternative to standard triweekly dosing. Longer intervals may reduce efficacy and require clinical validation.</p>

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Pharmacokinetic insights into atezolizumab SC: viability of extended dosing intervals beyond the standard regimen

  • 期刊论文

  • 发表日期：

    2026年3月6日

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  • Vicente Gimeno-Ballester,
  • Elena Herranz-Bayo,
  • Cristina Trigo-Vicente

摘要

Purpose

Atezolizumab is a monoclonal antibody against programmed cell death ligand 1 (PD-L1) used in oncology. With the intravenous formulation, the standard dose exceeds the established minimum effective concentration (MEC, 6 μg/mL). A subcutaneous (SC) triweekly formulation was recently introduced. This study aimed to predict SC atezolizumab exposure under extended dosing regimens using a population pharmacokinetic (PopPK) model.

Methods

This study used a PopPK in silico model based on data from the IMscin001 trial (SC atezolizumab in non-small cell lung cancer) to predict exposure for SC atezolizumab 1875 mg administered every 4, 5, 6, and 7 weeks (q4w–q7w). Simulations were performed in Monolix. Minimum concentrations after the first cycle (CMIN,1) and at steady state (CMIN,SS) were assessed in 1000 simulations per interval, with efficacy defined by 99% of simulations maintaining trough concentrations above the 6 μg/mL MEC.

Results

The model showed good agreement between simulated and observed plasma concentrations (PC), supporting its predictive performance. With q4w, CMIN,1 was 29.48 µg/mL and CMIN,SS was 34.42 µg/mL, both well above the MEC. Similar results were found for q5w (CMIN,1 at 18.13 µg/mL; CMIN,SS at 22.85 µg/mL). With q6w, PC remained above but close to the MEC, whereas q7w fell below this threshold.

Conclusions

Our PopPK model suggests that extending SC atezolizumab dosing to 4 or 5 weeks maintains therapeutic efficacy and could serve as a clinically viable alternative to standard triweekly dosing. Longer intervals may reduce efficacy and require clinical validation.