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

M. Burotto*, Z. Zvirbule, A. Mochalova, Y. Runglodvatana, L. Herraez-Baranda, S. N. Liu, P. Chan, E. Shearer-Kang, X. Liu, N. Tosti, J. A. Zanghi, B. Leutgeb, E. Felip

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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. Patients and methods: Eligible patients with locally advanced/metastatic non-small-cell lung cancer were randomised 2 : 1 to receive atezolizumab SC (1875 mg; n = 247) or IV (1200 mg; n = 124) every 3 weeks. The co-primary endpoints were cycle 1 observed trough serum concentration (Ctrough) and model-predicted area under the curve from days 0 to 21 (AUC0-21 d). The secondary endpoints were steady-state exposure, efficacy, safety, and immunogenicity. Exposure following atezolizumab SC was then compared with historical atezolizumab IV values across approved indications. Results: The study met both of its co-primary endpoints: cycle 1 observed Ctrough {SC: 89 μg/ml [coefficient of variation (CV): 43%] versus IV: 85 μg/ml (CV: 33%); geometric mean ratio (GMR), 1.05 [90% confidence interval (CI) 0.88-1.24]} and model-predicted AUC0-21 d [SC: 2907 μg d/ml (CV: 32%) versus IV: 3328 μg d/ml (CV: 20%); GMR, 0.87 (90% CI 0.83-0.92)]. Progression-free survival [hazard ratio 1.08 (95% CI 0.82-1.41)], objective response rate (SC: 12% versus IV: 10%), and incidence of anti-atezolizumab antibodies (SC: 19.5% versus IV: 13.9%) were similar between arms. No new safety concerns were identified. Ctrough and AUC0-21 d for atezolizumab SC were consistent with the other approved atezolizumab IV indications. Conclusions: Compared with IV, atezolizumab SC demonstrated noninferior drug exposure at cycle 1. Efficacy, safety, and immunogenicity were similar between arms and consistent with the known profile for atezolizumab IV. Similar drug exposure and clinical outcomes following SC and IV administration support the use of atezolizumab SC as an alternative to atezolizumab IV.

Original languageEnglish
Pages (from-to)693-702
Number of pages10
JournalAnnals of Oncology
Volume34
Issue number8
DOIs
StatePublished - Aug 2023
Externally publishedYes

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Publisher Copyright:
© 2023 The Author(s)

Keywords

  • atezolizumab
  • cancer immunotherapy
  • non-small-cell lung cancer
  • pharmacokinetics
  • recombinant human hyaluronidase
  • subcutaneous

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