{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:17:34Z","timestamp":1787793454801,"version":"build-2784847793"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008021","name":"Bristol-Myers Squibb Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Golcadomide is a potential first\u2010in\u2010class oral CELMoD\u2122 agent for the treatment of lymphoma. This study aims to develop model\u2010informed drug development (MIDD) approaches to support optimal dose selection of golcadomide in combination with immunotherapy rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R\u2010CHOP) in alignment with the U.S. Food and Drug Administration (FDA) Project Optimus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the ongoing Phase 1b study CC\u2010220\u2010DLBCL\u2010001 (NCT04884035), clinical safety, efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) data were collected across two dose levels (0.2 and 0.4\u2009mg) of golcadomide in combination with R\u2010CHOP. Integrated analyses, including population PK (popPK), PK\/PD and exposure\u2013response (E\u2013R) modelling analyses, were conducted to assess benefit\u2013risk profiles and to inform dose selection in the combination setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with 0.2\u2009mg, the 0.4\u2009mg dose of golcadomide in combination with R\u2010CHOP was associated with higher exposure and more rapid, deeper degradation of targeted protein Ikaros. In addition, a positive relationship was observed between exposure and end\u2010of\u2010treatment complete metabolic response (CMR). Except for grade 4 thrombocytopenia, no obvious E\u2013R trends were found for safety endpoints, including grade 3+ neutropenia, any grade febrile neutropenia and adverse events (AEs) leading to golcadomide dose modification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The integrated MIDD evaluation conducted in this study provided a quantitative and mechanism\u2010based rationale for the optimal dose selection of golcadomide in previously untreated aggressive B\u2010cell lymphoma. The findings also highlight the value of a systematic MIDD framework for dose optimization in alignment with FDA's Project Optimus initiative and provide an example for oncology drug dose selection in combination therapy settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70728","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:20:29Z","timestamp":1787790029000},"source":"Crossref","is-referenced-by-count":0,"title":["Model\u2010informed optimal dose selection of golcadomide in combination with R\u2010CHOP in patients with previously untreated aggressive B\u2010cell lymphoma"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9377-7497","authenticated-orcid":false,"given":"Xirong","family":"Zheng","sequence":"first","affiliation":[{"name":"Translational Medicine and Clinical Pharmacology Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiling","family":"Yu","sequence":"additional","affiliation":[{"name":"Translational Medicine and Clinical Pharmacology Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Translational Medicine and Clinical Pharmacology Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argyrios","family":"Gkasiamis","sequence":"additional","affiliation":[{"name":"Late Clinical Development Hematology Bristol Myers Squibb  Boudry Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Sudhindra","sequence":"additional","affiliation":[{"name":"Early Clinical Development Bristol Myers Squibb  Madison New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"Translational Medicine and Clinical Pharmacology Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Lamba","sequence":"additional","affiliation":[{"name":"Translational Medicine and Clinical Pharmacology Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wu","sequence":"additional","affiliation":[{"name":"Translational Medicine and Clinical Pharmacology Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp2109826"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3373"},{"key":"e_1_2_10_4_1","unstructured":"Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases \u2010 Guidance for industry.2024."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/17407745241232428"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201024\u20101836"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00371"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201015\u20101295"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.473"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102021\u2010148068"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/2643\u20103230.BCD\u201025\u20100059"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102024\u2010203185"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102024\u2010203181"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102024\u2010203131"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010180231"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010023\u201009850\u20102"},{"issue":"8","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1007\/s11095-022-03288-w","article-title":"Role of model\u2010informed drug development approaches in the lifecycle of drug development and regulatory decision\u2010making","volume":"39","author":"Madabushi R","year":"2022","journal-title":"Pharm Res"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007311111"},{"key":"e_1_2_10_19_1","unstructured":"WuF ZhengX PatahP et al.Population Pharmacokinetic Modeling for CC\u201099282 a Novel Cereblon E3 Ligase Modulator (CELMoD) Agent in Patients With Relapsed or Refractory Non\u2010Hodgkin Lymphoma. presented at: American Conference on Pharmacometrics (ACoP) 13th Annual Meeting;2022; 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