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This research supports the approved intravenous clinical dose regimen, summarizing the exposure\u2013response relationships for clinical safety and efficacy. A population pharmacokinetic model and <jats:italic>E<\/jats:italic><jats:sub>max<\/jats:sub> logistic regression exposure\u2013response models for safety and efficacy were developed using data from 439 patients with relapsed\/refractory non\u2010Hodgkin lymphoma and 159 patients with relapsed\/refractory follicular lymphoma, respectively, from a Phase I\/II study (NCT02500407). Data from 0.2 to 60\u2009mg across fixed dosing (Cohort A) and Cycle 1 step\u2010up dosing (Cohort B) were used. Exposure\u2013response models, using two\u2010cycle area\u2010under\u2010the\u2010concentration curve (AUC<jats:sub>0\u201342<\/jats:sub>) as the primary exposure endpoint, accurately depicted the complete response and objective response rate data across a 600\u2010fold AUC<jats:sub>0\u201342<\/jats:sub> range. The approved clinical dose regimen of 1\/2\/60\/30\u2009mg achieved near\u2010maximal efficacy, with model\u2010estimated CR and ORR (90% confidence interval) of 63.1% (49.7\u201375.0) and 79.1% (69.1\u201387.7), respectively. The exposure\u2013response analysis for Grade\u2009\u2265\u20092 cytokine release syndrome identified receptor occupancy (%) within the first two cycles as a driver, with CRS dissipating beyond the first dosing cycle. No exposure\u2010dependent increases were observed for other serious adverse events, including neutropenia and infections. The approved intravenous step\u2010up dose regimen (i.e., step doses of 1 and 2\u2009mg on Day 1 and 8, respectively) mitigated severe CRS risk, allowing safe administration of loading (60\u2009mg) and target doses (30\u2009mg every 3\u2009weeks) to achieve a favorable benefit\u2013risk profile.<\/jats:p>","DOI":"10.1002\/cpt.3445","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T08:27:35Z","timestamp":1727425655000},"page":"465-474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Novel Step\u2010Up Dosage Regimen for Enhancing the Benefit\u2010to\u2010Risk Ratio of Mosunetuzumab in Relapsed or Refractory Follicular Lymphoma"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9590-3450","authenticated-orcid":false,"given":"Chi\u2010Chung","family":"Li","sequence":"first","affiliation":[{"name":"Genentech, Inc.  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