Population Pharmacokinetics and Exposure‐Response of Subcutaneous Atezolizumab in Patients With Non‐Small Cell Lung Cancer

ABSTRACT IMscin001 is a two‐part dose‐finding (Phase Ib) and ‐confirmation (Phase III) study to evaluate atezolizumab pharmacokinetics of subcutaneous (SC) compared with intravenous (IV) administration in patients with locally advanced or metastatic non‐small cell lung cancer (NSCLC). The objectives...

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Vydáno v:	CPT: pharmacometrics and systems pharmacology Ročník 14; číslo 4; s. 726 - 737
Hlavní autoři:	Chan, Phyllis, Liu, Stephanie N., Gosselin, Nathalie, Sauve, Zacharie, Marchand, Mathilde, Lin, Alyse, Herraez‐Baranda, Luis, Zanghi, James, Shearer‐Kang, Esther, Liu, Xiaoyan, Wu, Benjamin, Chanu, Pascal
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States John Wiley & Sons, Inc 01.04.2025 John Wiley and Sons Inc Wiley
Témata:	Abdomen Administration, Intravenous Adult Aged Antibodies, Monoclonal, Humanized - administration & dosage Antibodies, Monoclonal, Humanized - adverse effects Antibodies, Monoclonal, Humanized - pharmacokinetics Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacokinetics Carcinoma, Non-Small-Cell Lung - drug therapy Cell death Dose-Response Relationship, Drug Drug development Drug dosages Female Humans Injections, Subcutaneous Lung cancer Lung Neoplasms - drug therapy Male Metastasis Middle Aged Models, Biological Patients Pharmacokinetics Population
ISSN:	2163-8306, 2163-8306
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Shrnutí:	ABSTRACT IMscin001 is a two‐part dose‐finding (Phase Ib) and ‐confirmation (Phase III) study to evaluate atezolizumab pharmacokinetics of subcutaneous (SC) compared with intravenous (IV) administration in patients with locally advanced or metastatic non‐small cell lung cancer (NSCLC). The objectives of the current analyses were to characterize the population pharmacokinetics (popPK) of atezolizumab and to determine the relationship between atezolizumab exposure and safety and efficacy endpoints in IMscin001. A previously validated IV popPK model was extended to add SC absorption parameters using SC and IV data from Phase Ib and Phase III of IMscin001 (N = 435), and covariate effects were investigated on the SC absorption parameters. The exposure‐response (ER) investigation was performed using SC data following 1875 mg every three weeks (q3w) administration in the Phase III portion of IMscin001 (N = 246). The clinical endpoints were objective response rate, progression‐free survival, or overall survival for efficacy, serious adverse events, special interest adverse events, Grades 3–5 adverse events, infusion‐related reaction, or injection site reactions for safety. Atezolizumab SC absorption was characterized by a first‐order absorption with a bioavailability of 71.8% and an absorption rate constant of 0.304 day−1. The extended popPK model was adequate to predict atezolizumab PK after IV and SC administrations and to predict individual exposure metrics. For all efficacy and safety endpoints, atezolizumab exposure was not statistically significant (p‐value > 0.05) in the ER models. The non‐inferior popPK exposure and flat ER results supported atezolizumab SC dose at 1875 mg q3w.
Bibliografie:	The authors received no specific funding for this work. Funding ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Funding: The authors received no specific funding for this work.
ISSN:	2163-8306 2163-8306
DOI:	10.1002/psp4.13310