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The contribution of age\u2010associated differences (e.g., ontogeny) beyond body\u2010size differences in the pediatric PKs of mAbs has not been comprehensively evaluated. In this study, the population PK of two mAbs (nivolumab and ipilimumab) in pediatric oncology patients were characterized. The effects of age\u2010related covariates on nivolumab or ipilimumab PKs were assessed using data from 13 and 10 clinical studies, respectively, across multiple tumor types, including melanoma, lymphoma, central nervous system tumors (CNSTs), and other solid tumors. Clearance was lower in pediatric patients (aged 1\u201317\u2009years) with solid tumors or CNST than in adults after adjusting for other covariates, including the effect of body size. In contrast, clearance was similar in pediatric patients with lymphoma to that in adults with lymphoma. The pediatric effects characterized have increased the accuracy of the predictions of the model, facilitating its use in subsequent exposure comparisons between pediatric and adult patients, as well as for exposure\u2013response analyses to inform pediatric dosing. This study approach may be applicable to the optimization of pediatric dosing of other mAbs and possibly other biologics.<\/jats:p>","DOI":"10.1002\/psp4.13098","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T06:03:42Z","timestamp":1703052222000},"page":"476-493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nivolumab and ipilimumab population pharmacokinetics in support of pediatric dose recommendations\u2014Going beyond the body\u2010size effect"],"prefix":"10.1002","volume":"13","author":[{"given":"Zheyi","family":"Hu","sequence":"first","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihang","family":"Liu","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-0134","authenticated-orcid":false,"given":"Yue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Du","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lora","family":"Hamuro","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Shen","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2140-1455","authenticated-orcid":false,"given":"Amit","family":"Roy","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17670-y"},{"key":"e_1_2_10_3_1","unstructured":"US Food and Drug Administration (USFDA).Considerations for the inclusion of adolescent patients in adult oncology clinical trials.2019.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/considerations\u2010inclusion\u2010adolescent\u2010patients\u2010adult\u2010oncology\u2010clinical\u2010trials. 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[Abstract PI\u2010028 2021] American Society for Clinical Pharmacology & Therapeutics (ASCPT) Annual Meeting; March 22\u201324 2021; Atlanta GA USA."},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239"},{"key":"e_1_2_10_20_1","unstructured":"YERVOY (ipilimumab). [Prescribing information. ]. Bristol\u2010Myers Squibb Company Princeton NJ USA2022.https:\/\/packageinserts.bms.com\/pi\/pi_yervoy.pdf. Accessed March 28 2023"},{"key":"e_1_2_10_21_1","unstructured":"YERVOY (ipilimumab). [Summary of product characteristics] Bristol\u2010Myers Squibb Company Uxbridge UK.2022.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/yervoy\u2010epar\u2010product\u2010information_en.pdf. Accessed March 28 2023"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12477"},{"key":"e_1_2_10_23_1","unstructured":"Centers for Disease Control and Prevention (CDC). National Health and Nutrition Examination Survey (NHANES) Database. 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