{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:01:55Z","timestamp":1790168515267,"version":"4.1.0"},"reference-count":9,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"abstract":"<jats:p>\n                    A novel model\u2010informed drug development (MIDD) approach was employed to derive the coprimary endpoints (time\u2010averaged serum concentration over 28\u2009days [C\n                    <jats:sub>avgd28<\/jats:sub>\n                    ] and minimum serum concentration at steady state [C\n                    <jats:sub>minss<\/jats:sub>\n                    ]) of the phase III CheckMate 67T study (NCT04810078). This approach also facilitated bridging to alternative subcutaneous (SC) dosing regimens and existing intravenous (IV) nivolumab monotherapy and combination indications. Individual exposures were derived via a population pharmacokinetic (popPK) analysis to establish pharmacokinetic (PK) noninferiority of nivolumab 1200\u2009mg SC every 4\u2009weeks (Q4W) vs. nivolumab 3\u2009mg\/kg IV every 2\u2009weeks (Q2W). Bridging to additional indications leveraged previously established nivolumab IV popPK models with the incorporation of SC components. Nivolumab population SC absorption rate constant and bioavailability were estimated to be 0.295\u2009day\n                    <jats:sup>\u22121<\/jats:sup>\n                    and 78.8%, respectively. Geometric means of C\n                    <jats:sub>avgd28<\/jats:sub>\n                    and C\n                    <jats:sub>minss<\/jats:sub>\n                    for 1200\u2009mg SC Q4W exceeded those for 3\u2009mg\/kg IV Q2W but remained below those for 10\u2009mg\/kg IV Q2W, a regimen used regularly to define the exposure safety margins for nivolumab. Simulation\u2010based PK bridging analyses showed that nivolumab SC regimens produced consistently higher exposures than approved nivolumab IV regimens across solid tumor indications, while maintaining exposures below the established safety margin. The MIDD approach provided an integrated and computationally efficient framework to characterize nivolumab SC\/IV PK. Simulation\u2010based analyses confirmed comparable benefit\u2013risk profiles of nivolumab SC in adults across solid tumor indications and led to FDA approval of nivolumab SC in existing adult IV indications (except for nivolumab in combination with ipilimumab).\n                  <\/jats:p>","DOI":"10.1002\/cpt.70481","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:10:57Z","timestamp":1790165457000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Model\u2010based clinical pharmacology profiling of subcutaneous nivolumab in renal cell carcinoma: Bridging to alternative dosing regimens and indications"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-0134","authenticated-orcid":false,"given":"Yue","family":"Zhao","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheyi","family":"Hu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Gibson","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Vezina","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna G.","family":"Kondic","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Bristol Myers Squibb  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"e_1_2_11_1_1","unstructured":"Bristol Myers Squibb.OPDIVO QVANTIG\u2122 (nivolumab and hyaluronidase\u2010nvhy) [package insert]Princeton NJ. (2026) <https:\/\/packageinserts.bms.com\/pi\/pi_opdivo\u2010qvantig.pdf> Accessed August 12 2026."},{"key":"e_1_2_11_2_1","first-page":"923","article-title":"The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection","volume":"9","author":"Jin J.F.","year":"2015","journal-title":"Patient Prefer. Adherence"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.annonc.2024.09.002","article-title":"Subcutaneous versus intravenous nivolumab for renal cell carcinoma","volume":"36","author":"Albiges L.","year":"2025","journal-title":"Ann. Oncol."},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s10928-020-09695-z","article-title":"Prior information for population pharmacokinetic and pharmacokinetic\/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine","volume":"47","author":"Chan Kwong A.H.P.","year":"2020","journal-title":"J. Pharmacokinet. Pharmacodyn."},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/cpt.3148","article-title":"Model\u2010based dose selection of subcutaneous nivolumab in patients with advanced solid tumors","volume":"115","author":"Zhao Y.","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1002\/psp4.70120","article-title":"Model\u2010informed drug development of subcutaneous nivolumab: comparison of pharmacokinetic analysis methodologies using clinical trial simulation","volume":"14","author":"Zhao Y.","year":"2025","journal-title":"CPT Pharmacometrics Syst. Pharmacol."},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2025-011918","article-title":"Pharmacokinetics and safety of subcutaneous nivolumab: results from the phase 1\/2 CheckMate 8KX study","volume":"13","author":"Lonardi S.","year":"2025","journal-title":"J. Immunother. Cancer"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/psp4.12143","article-title":"Model\u2010based population pharmacokinetic analysis of nivolumab in patients with solid tumors","volume":"6","author":"Bajaj G.","year":"2017","journal-title":"CPT Pharmacometrics Syst. Pharmacol."},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1093\/annonc\/mdz037","article-title":"Model\u2010informed drug development approach supporting approval of the 4\u2010week (Q4W) dosing schedule for nivolumab (Opdivo) across multiple indications: a regulatory perspective","volume":"30","author":"Bi Y.","year":"2019","journal-title":"Ann. Oncol."}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70481","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70481","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70481","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:11:00Z","timestamp":1790165460000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":9,"alternative-id":["10.1002\/cpt.70481"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70481","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]},"assertion":[{"value":"2026-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cpt.70481"}}