{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:05:56Z","timestamp":1787843156449,"version":"build-2784847793"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Lessons Learned<\/jats:title><jats:p>The overall safety profiles of ipilimumab 3 mg\/kg and 10 mg\/kg administered every 3\u2009weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified. The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg\/kg and 10 mg\/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg\/kg and 10 mg\/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>This phase I, open-label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Of 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg\/kg, and 14 patients received 10 mg\/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as \u201cother.\u201d During the induction phase, patients received ipilimumab (3 mg\/kg, i.v.), on day 1 of a 3-week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg\/kg, i.v.) on day 1 of a 12-week cycle, to a maximum of 3\u2009years or PD. Considering the co-primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose-limiting toxicities during the 42-day observation period to proceed with a new cohort of nine patients at 10 mg\/kg.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ipilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1\u20132 and experienced by 11 patients treated with 3 mg\/kg and 14 patients treated with 10 mg\/kg. There were no new safety concerns. Incidence of anti-ipilimumab antibodies was low (1 of 10 in the 3 mg\/kg patients and 2 of 13 in the 10 mg\/kg patients) and without safety implications. In the 3 mg\/kg group, 8 of 11 patients had PD. In the 10 mg\/kg group (all NPC, 0\u2009MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg\/kg and two at 10 mg\/kg).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Ipilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/onco.13577","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T18:34:39Z","timestamp":1603737279000},"page":"e549-e566","source":"Crossref","is-referenced-by-count":5,"title":["A Phase I Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors"],"prefix":"10.1093","volume":"26","author":[{"given":"Yuxiang","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Clinical Research, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfeng","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai Praneeth","family":"Bathena","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Lawrenceville, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amol","family":"Tendolkar","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Lawrenceville, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Sheng","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Lawrenceville, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,11]]},"reference":[{"key":"2021122512175198700_onco13577-bib-0001","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S1470-2045(17)30231-0","article-title":"Ipilimumab 10 mg\/kg versus ipilimumab 3 mg\/kg in patients with unresectable or metastatic melanoma: A randomised, double-blind, multicentre, phase 3 trial","volume":"18","author":"Ascierto","year":"2017","journal-title":"Lancet Oncol"},{"key":"2021122512175198700_onco13577-bib-0002","first-page":"29","volume-title":"Early Phase Cancer Immunotherapy","author":"Lamb","year":"2017"},{"key":"2021122512175198700_onco13577-bib-0003","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/978-1-4939-2047-1_16","volume-title":"Targeted Therapies for Solid Tumors: A Handbook for Moving Toward New Frontiers in Cancer Treatment","author":"Fanale","year":"2015"},{"key":"2021122512175198700_onco13577-bib-0004","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s40257-013-0025-9","article-title":"Optimal management of metastatic melanoma: Current strategies and future directions","volume":"14","author":"Batus","year":"2013","journal-title":"Am J Clin Dermatol"},{"key":"2021122512175198700_onco13577-bib-0005","first-page":"7","article-title":"Randomized phase I pharmacokinetic study of ipilimumab with or without one of two different chemotherapy regimens in patients with untreated advanced melanoma","volume":"13","author":"Weber","year":"2013","journal-title":"Cancer Immun"},{"key":"2021122512175198700_onco13577-bib-0006","author":"Yervoy (ipilimumab) [package insert]","year":"2020"},{"key":"2021122512175198700_onco13577-bib-0007","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/cts.12567","article-title":"Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development","volume":"11","author":"Ovacik","year":"2018","journal-title":"Clin Transl Sci"},{"key":"2021122512175198700_onco13577-bib-0008","doi-asserted-by":"crossref","first-page":"295","DOI":"10.2165\/11319980-000000000-00000","article-title":"CYP-mediated therapeutic protein drug interactions: clinical findings, proposed mechanisms, and regulatory implications","volume":"49","author":"Lee","year":"2010","journal-title":"Clin Pharmacokinet"},{"key":"2021122512175198700_onco13577-bib-0009","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2165\/11531280-000000000-00000","article-title":"Clinical pharmacokinetics of therapeutic monoclonal antibodies","volume":"49","author":"Keizer","year":"2010","journal-title":"Clin Pharmacokinet"},{"key":"2021122512175198700_onco13577-bib-0010","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/onco.13577","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/onco.13577","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/26\/4\/e549\/41923760\/oncolo_26_4_e549.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/26\/4\/e549\/41923760\/oncolo_26_4_e549.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T16:46:24Z","timestamp":1696956384000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/26\/4\/e549\/6445550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,11]]},"references-count":10,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,11,11]]},"published-print":{"date-parts":[[2021,4,1]]}},"URL":"https:\/\/doi.org\/10.1002\/onco.13577","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,4,1]]},"published":{"date-parts":[[2020,11,11]]}}}