Population pharmacokinetics and exposure–response analyses of polatuzumab vedotin in patients with previously untreated DLBCL from the POLARIX study

Autor: Rong Deng, Leonid Gibiansky, Tong Lu, Christopher R. Flowers, Laurie H. Sehn, Qi Liu, Priya Agarwal, Michael Z. Liao, Randall Dere, Calvin Lee, Gabriel Man, Jamie Hirata, Chunze Li, Dale Miles
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: CPT: Pharmacometrics & Systems Pharmacology, Vol 13, Iss 6, Pp 1055-1066 (2024)
Druh dokumentu: article
ISSN: 2163-8306
DOI: 10.1002/psp4.13141
Popis: Abstract Polatuzumab vedotin is a CD79b‐directed antibody–drug conjugate that targets B cells and delivers the cytotoxic payload monomethyl auristatin E (MMAE). The phase III POLARIX study (NCT03274492) evaluated polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R‐CHP) as first‐line treatment of diffuse large B‐cell lymphoma (DLBCL). To examine dosing decisions for this regimen, population pharmacokinetic (popPK) analysis, using a previously developed popPK model, and exposure–response (ER) analysis, were performed. The popPK analysis showed no clinically meaningful relationship between cycle 6 (C6) antibody‐conjugated (acMMAE)/unconjugated MMAE area under the concentration–time curve (AUC) or maximum concentration, and weight, sex, ethnicity, region, mild or moderate renal impairment, mild hepatic impairment, or other patient and disease characteristics. In the ER analysis, C6 acMMAE AUC was significantly associated with longer progression‐free and event‐free survival (both p = 0.01). An increase of
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