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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Veröffentlicht in:CPT: pharmacometrics and systems pharmacology Jg. 14; H. 4; S. 726 - 737
Hauptverfasser: 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
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States John Wiley & Sons, Inc 01.04.2025
John Wiley and Sons Inc
Wiley
Schlagworte:
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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Zusammenfassung: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.
Bibliographie:The authors received no specific funding for this work.
Funding
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Funding: The authors received no specific funding for this work.
ISSN:2163-8306
2163-8306
DOI:10.1002/psp4.13310