KEY TAKEAWAYS
- A phase 1b/3 IMscin001 trial aimed to establish a subcutaneous dose of atezolizumab that would result in a serum Ctrough equivalent to that intravenous administration.
- The study involved the administration of subcutaneous atezolizumab to patients enrolled in three cohorts.
- The subcutaneous administration of atezolizumab at 1800 mg every 3 weeks and 1200 mg every 2 weeks yielded comparable Ctrough.
- The abdominal subcutaneous injection resulted in a comparatively lower exposure than the thigh.
- The initiation of Part 2 (Phase 3) will demonstrate that the pharmacokinetic exposure of subcutaneous atezolizumab is not inferior to that of intravenous administration.
The administration of intravenous (IV) atezolizumab has been sanctioned for treating non-small cell lung and other malignancies. The development of subcutaneous (SC) atezolizumab co-formulated with recombinant human hyaluronidase, a permeation enhancer for SC dispersion and absorption, aims to enhance treatment options, alleviate the burden, and optimize efficiency for patients and practitioners. The clinical trial IMscin001 (NCT03735121) is a two-part, open-label, global, multicenter, phase 1b/3 investigation that aimed to assess the pharmacokinetics (PK), safety, and efficacy of subcutaneous atezolizumab. The primary goal of phase 1b, part 1, was to establish a subcutaneous dose of atezolizumab that would result in a serum trough concentration (Ctrough) equivalent to that achieved through intravenous administration.
The study involved the administration of SC atezolizumab to patients enrolled in three cohorts. Cohort 1 received a single dose of 1800 mg at the thigh. Cohort 2 received 1200 mg at the thigh every two weeks for three cycles. Cohort 3 received 1800 mg at the abdomen during cycle 1, followed by 1800 mg at the thigh every three weeks during cycles 2 and 3. The patient received IV atezolizumab at a dose of 1200 mg every 3 weeks in the following cycles until clinical benefit was no longer observed. The subcutaneous administration of atezolizumab at a dose of 1800 mg every 3 weeks and 1200 mg every 2 weeks yielded comparable Ctrough and area under the curve values during the first cycle compared to the intravenous atezolizumab reference. Additionally, this mode of administration was well-tolerated and demonstrated a safety profile consistent with the established intravenous formulation. The abdominal subcutaneous injection resulted in a comparatively lower exposure (20% for Ctrough, 28% for maximum concentration, and 27% for area under the concentration-time curve from time 0 to day 21) than the thigh. The population pharmacokinetic modeling approach was utilized to analyze the SC and IV PK data in Part 1, followed by simulations. The initiation of Part 2 (Phase 3) will demonstrate that the pharmacokinetic exposure of subcutaneous atezolizumab is not inferior to that of intravenous administration.
Source: https://pubmed.ncbi.nlm.nih.gov/33788415/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03735121
Felip E, Burotto M, Zvirbule Z, Herraez-Baranda LA, Chanu P, Kshirsagar S, Maiya V, Chan P, Pozzi E, Marchand M, Monchalin M, Tanaka K, Tosti N, Wang B, Restuccia E. Results of a Dose-Finding Phase 1b Study of Subcutaneous Atezolizumab in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer. Clin Pharmacol Drug Dev. 2021 Oct;10(10):1142-1155. doi: 10.1002/cpdd.936. Epub 2021 Mar 31. PMID: 33788415; PMCID: PMC8518371.
