Results of a Dose-Finding Phase 1b Study of Subcutaneous Atezolizumab in Patients With Locally Advanced or Metastatic Non–Small Cell Lung Cancer

Enriqueta Felip*, Mauricio Burotto, Zanete Zvirbule, Luis A. Herraez-Baranda, Pascal Chanu, Smita Kshirsagar, Vidya Maiya, Phyllis Chan, Emanuela Pozzi, Mathilde Marchand, Marion Monchalin, Kunihiko Tanaka, Nadia Tosti, Bei Wang, Eleonora Restuccia

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Intravenous (IV) atezolizumab is approved for non–small cell lung and other cancers. Subcutaneous (SC) atezolizumab coformulated with recombinant human hyaluronidase, a permeation enhancer for SC dispersion and absorption, is being developed to improve treatment options, reduce burden, and increase efficiency for patients and practitioners. IMscin001 (NCT03735121), a 2-part, open-label, global, multicenter, phase 1b/3 study, is evaluating the pharmacokinetics (PK), safety, and efficacy of SC atezolizumab. The part 1 (phase 1b) objective was determination of an SC atezolizumab dose yielding a serum trough concentration (Ctrough) comparable with IV. Patients enrolled in 3 cohorts received SC atezolizumab 1800 mg (thigh) once (cohort 1), 1200 mg (thigh) every 2 weeks for 3 cycles (cohort 2), or 1800 mg (abdomen) every 3 weeks cycle 1, then cycles 2 and 3 (thigh) every 3 weeks (cohort 3). In subsequent cycles, IV atezolizumab 1200 mg every 3 weeks was administered until loss of clinical benefit. SC atezolizumab 1800 mg every 3 weeks and 1200 mg every 2 weeks provided similar Ctrough and area under the curve values in cycle 1 to the corresponding IV atezolizumab reference, was well tolerated, and exhibited a safety profile consistent with the established IV formulation. Exposure following SC injection in the abdomen was lower (20%, 28%, and 27% for Ctrough, maximum concentration, and area under the concentration-time curve from time 0 to day 21, respectively) than in the thigh. Part 1 SC and IV PK data were analyzed using a population PK modeling approach, followed by simulations. Part 2 (phase 3) will now be initiated to demonstrate that SC atezolizumab PK exposure is not lower than that of IV.

Original languageEnglish
JournalClinical Pharmacology in Drug Development
DOIs
StateAccepted/In press - 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology

Keywords

  • atezolizumab
  • hyaluronanidase
  • NSCLC
  • pharmacokinetics
  • subcutaneous

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