Results of a Dose‐Finding Phase 1b Study of Subcutaneous Atezolizumab in Patients With Locally Advanced or Metastatic Non–Small Cell Lung Cancer. Issue 10 (31st March 2021)

• Record Type: Journal Article
• Authors: Felip, Enriqueta; Burotto, Mauricio; Zvirbule, Zanete; Herraez‐Baranda, Luis A.; Chanu, Pascal; Kshirsagar, Smita; Maiya, Vidya; Chan, Phyllis; Pozzi, Emanuela; Marchand, Mathilde; Monchalin, Marion; Tanaka, Kunihiko; Tosti, Nadia; Wang, Bei; Restuccia, Eleonora
• Is Part Of: Clinical pharmacology in drug development. Volume 10:Issue 10(2021)
• Page Start: 1142
• Page End: 1155
• Publication Date: 2021-03-31
• Subjects: atezolizumab -- hyaluronanidase -- NSCLC -- pharmacokinetics -- subcutaneous; Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.936
• Languages: English
• ISSNs: 2160-7648

Abstract

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.