{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:07:30Z","timestamp":1773032850834,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study introduces a novel drug\u2010disease modeling framework designed to assess the benefit\u2013risk balance of antibody\u2010drug conjugates (ADC) in oncology. The framework integrates dose levels, pharmacokinetics, tumor growth dynamics, progression\u2010free survival (PFS), and dose\u2010adjusted adverse events. We demonstrated this through its application to tusamitamab ravtansine (Tusa), an ADC targeting Carcinoembryonic Antigen\u2010Related Cell Adhesion Molecule 5 in non\u2010squamous non\u2010small cell lung cancer (nsq NSCLC). We developed our model using phase I trial safety data from 254 patients (doses: 5\u2013190\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ) and efficacy data from 88 nsq NSCLC patients (dose 100\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ). This model accurately predicted phase III outcomes for the Tusa arm via an iterative simulation. Using phase III baseline characteristics, simulations of Tusa doses comparing three dose levels (80, 100, and 120\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    every 2\u2009weeks) revealed a critical trade\u2010off: while higher doses increased response rates, they also substantially increased corneal toxicity without improving survival. These findings demonstrate how early\u2010phase data can inform optimal dose selection by quantifying benefit\u2013risk. This robust framework and methodology is generalizable beyond Tusa, offering value to support dose selection and trial decision\u2010making in oncology drug development.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70190","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T09:21:26Z","timestamp":1769678486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Drug\u2010Disease Modeling Framework for Oncology Benefit\u2013Risk Evaluation: Application to Tusamitamab Ravtansine"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6792-2526","authenticated-orcid":false,"given":"Marc","family":"Cerou","sequence":"first","affiliation":[{"name":"Translational Medicine Unit, Quantitative Pharmacology Sanofi  Gentilly France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9865-8959","authenticated-orcid":false,"given":"Christine","family":"Veyrat\u2010Follet","sequence":"additional","affiliation":[{"name":"Translational Medicine Unit, Quantitative Pharmacology Sanofi  Gentilly France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Fliscounakis\u2010Huynh","sequence":"additional","affiliation":[{"name":"Translational Medicine Unit, Quantitative Pharmacology Sanofi, on Behalf of IT&amp;M Stats  Gentilly France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3081-8201","authenticated-orcid":false,"given":"Clemence","family":"Pouzin","sequence":"additional","affiliation":[{"name":"Translational Medicine Unit, Development Projects Sanofi  Vitry sur Seine France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7381-8657","authenticated-orcid":false,"given":"Nathalie","family":"Fagniez","sequence":"additional","affiliation":[{"name":"Translational Medicine Unit, Development Projects Sanofi  Vitry sur Seine France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7350-0120","authenticated-orcid":false,"given":"Frano","family":"Mihaljevic","sequence":"additional","affiliation":[{"name":"Simulations Plus, Lixoft Division  Antony France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustapha","family":"Chadjaa","sequence":"additional","affiliation":[{"name":"Clinical Development Sanofi, R&amp;D  Vitry\u2010sur\u2010Seine France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9150-9886","authenticated-orcid":false,"given":"Emmanuelle","family":"Comets","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 et Universit\u00e9 Sorbonne Paris Nord, IAME, Inserm  Paris France"},{"name":"Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) \u2013 UMR_S 1085  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5239-6399","authenticated-orcid":false,"given":"Hoai\u2010Thu","family":"Thai","sequence":"additional","affiliation":[{"name":"Translational Medicine Unit, Quantitative Pharmacology Sanofi  Gentilly 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