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We developed a joint model integrating pharmacokinetics, pharmacodynamics, and Deauville score to evaluate alternative dosing strategies for a CD3\u2009\u00d7\u2009CD20 bispecific antibody, epcoritamab, as monotherapy in relapsed or refractory (R\/R) large B\u2010cell lymphoma (LBCL) after \u22652 lines of systemic therapy. The model was developed using clinical data from 165 patients and simultaneously described plasma epcoritamab concentrations, tumor burden dynamics, and longitudinal Deauville scores. Simulations were conducted in 1,000 virtual patients to evaluate three post\u2010complete response (CR) dosing strategies: continuous, fixed\u2010duration, and stop\u2010at\u2010CR. Responder subgroups were defined based on CR durability, and predictors of patients likely to require continuous treatment were explored. Simulations indicated that continued epcoritamab treatment after CR was associated with higher simulated CR rates over the long term, with simulated 2\u2010year CR rates of 46.4% (continuous), 37.2% (fixed\u2010duration), and 27.0% (stop\u2010at\u2010CR). Exploratory analyses suggested that indicators of residual disease, such as limited early tumor reduction and elevated circulating tumor DNA levels, help identify patients most likely to benefit from continuous treatment. This modeling framework provides a quantitative approach for evaluating alternative dosing strategies for epcoritamab monotherapy in R\/R LBCL and supports the potential value of continuous therapy in maintaining long\u2010term CR, as suggested by model\u2010based simulations. However, this study focuses solely on efficacy outcomes; therefore, further validation and incorporation of safety outcomes are needed to fully support clinical decision\u2010making and regimen optimization.<\/jats:p>","DOI":"10.1002\/cpt.70336","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:01:34Z","timestamp":1778850094000},"page":"692-701","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Model\u2010Informed Dosing Strategies for Epcoritamab Monotherapy in Relapsed or Refractory Large B\u2010Cell Lymphoma"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9925-5892","authenticated-orcid":false,"given":"Xiaozhi","family":"Liao","sequence":"first","affiliation":[{"name":"University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8657-9436","authenticated-orcid":false,"given":"Tommy","family":"Li","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6997-5533","authenticated-orcid":false,"given":"Steven","family":"Xu","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0959-2025","authenticated-orcid":false,"given":"Mohamed\u2010Eslam F.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"AbbVie  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7966-7980","authenticated-orcid":false,"given":"Mahipal","family":"Sinnollareddy","sequence":"additional","affiliation":[{"name":"AbbVie  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Gupta","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Wielgos\u2010Bonvallet","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Steele","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Sacchi","sequence":"additional","affiliation":[{"name":"Genmab  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3974-9073","authenticated-orcid":false,"given":"Yanguang","family":"Cao","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-1836"},{"key":"e_1_2_10_2_1","unstructured":"FDA Oncology Center of Excellence.Project Optimus: Reforming the dose optimization and dose selection paradigm in oncology<https:\/\/www.fda.gov\/about\u2010fda\/oncology\u2010center\u2010excellence\/project\u2010optimus> (2024). 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