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Open Access 05-04-2024 | Pharmacokinetics | Original Research Article

Population Pharmacokinetics of Sacituzumab Govitecan in Patients with Metastatic Triple-Negative Breast Cancer and Other Solid Tumors

Authors: Abhishek G. Sathe, Indrajeet Singh, Pratap Singh, Paul M. Diderichsen, Xiaohui Wang, Peter Chang, Atiya Taqui, See Phan, Sandhya Girish, Ahmed A. Othman

Published in: Clinical Pharmacokinetics

Abstract

Background and Objective

Sacituzumab govitecan (SG) is an antibody–drug conjugate composed of an antibody with affinity for Trop-2 coupled to SN-38 via hydrolyzable linker. SG is approved for patients with metastatic triple-negative breast cancer (mTNBC) who have received two or more prior chemotherapies (at least one in a metastatic setting) and for patients with pretreated hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2–) metastatic breast cancer.

Methods

In these analyses, the pharmacokinetics of SG, free SN-38, and total antibody (tAB) were characterized using data from 529 patients with mTNBC or other solid tumors across two large clinical trials (NCT01631552; ASCENT, NCT02574455). Three population pharmacokinetic models were constructed using non-linear mixed-effects modeling; clinically relevant covariates were evaluated to assess their impact on exposure. Models for SG and tAB were developed independently whereas free SN-38 was sequentially generated via a first-order release process from SG.

Results

Pharmacokinetics of the three analytes were each described by a two-compartment model with estimated body weight-based scaling exponents for clearance and volume. Typical parameter estimates for clearance and steady-state volume of distribution were 0.133 L/h and 3.68 L for SG and 0.0164 L/h and 4.26 L for tAB, respectively. Mild-to-moderate renal impairment, mild hepatic impairment, age, sex, baseline albumin level, tumor type, UGT1A1 genotype, or Trop-2 expression did not have a clinically relevant impact on exposure for any of the three analytes.

Conclusions

These analyses support the approved SG dosing regimen of 10 mg/kg as intravenous infusion on days 1 and 8 of 21-day cycles and did not identify a need for dose adjustment based on evaluated covariates or disease characteristics.

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Title: Population Pharmacokinetics of Sacituzumab Govitecan in Patients with Metastatic Triple-Negative Breast Cancer and Other Solid Tumors
Authors: Abhishek G. Sathe
Indrajeet Singh
Pratap Singh
Paul M. Diderichsen
Xiaohui Wang
Peter Chang
Atiya Taqui
See Phan
Sandhya Girish
Ahmed A. Othman
Publication date: 05-04-2024
Publisher: Springer International Publishing
Keywords: Pharmacokinetics
Breast Cancer
Breast Cancer
Solid Tumor
Published in: Clinical Pharmacokinetics
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-024-01366-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Population Pharmacokinetics of Sacituzumab Govitecan in Patients with Metastatic Triple-Negative Breast Cancer and Other Solid Tumors

Abstract

Background and Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and Objective

Methods

Results

Conclusions

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