{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:19:31Z","timestamp":1791047971720,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mosunetuzumab (Mosun) is a CD20xCD3 T\u2010cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. The approved step\u2010up dose regimen of 1\/2\/60\/30\u2009mg IV is designed to mitigate cytokine release syndrome (CRS) and maximize efficacy in early cycles. A population pharmacokinetic (popPK) model was developed from 439 patients with relapsed\/refractory B\u2010Cell Non\u2010Hodgkin lymphoma receiving Mosun IV monotherapy, including fixed dosing (0.05\u20132.8\u2009mg IV every 3\u2009weeks (q3w)) and Cycle 1 step\u2010up dosing groups (0.4\/1\/2.8\u20131\/2\/60\/30\u2009mg IV q3w). Prior to Mosun treatment, ~50% of patients had residual levels of anti\u2010CD20 drugs (e.g., rituximab or obinutuzumab) from prior treatment. CD20 receptor binding dynamics and rituximab\/obinutuzumab PK were incorporated into the model to calculate the Mosun CD20 receptor occupancy percentage (RO%) over time. A two\u2010compartment model with time\u2010dependent clearance (CL) best described the data. The typical patient had an initial CL of 1.08\u2009L\/day, transitioning to a steady\u2010state CL of 0.584\u2009L\/day. Statistically relevant covariates on PK parameters included body weight, albumin, sex, tumor burden, and baseline anti\u2010CD20 drug concentration; no covariate was found to have a clinically relevant impact on exposure at the approved dose. Mosun CD20 RO% was highly variable, attributed to the large variability in residual baseline anti\u2010CD20 drug concentration (median\u2009=\u200910\u2009\u03bcg\/mL). The 60\u2009mg loading doses increased Mosun CD20 RO% in Cycle 1, providing efficacious exposures in the presence of the competing anti\u2010CD20 drugs. PopPK model simulations, investigating Mosun dose delays, informed treatment resumption protocols to ensure CRS mitigation.<\/jats:p>","DOI":"10.1111\/cts.13825","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T09:30:35Z","timestamp":1716975035000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Population pharmacokinetics and CD20 binding dynamics for mosunetuzumab in relapsed\/refractory B\u2010cell non\u2010Hodgkin lymphoma"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1093-0661","authenticated-orcid":false,"given":"Brendan","family":"Bender","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Genentech Inc.  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