{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:55:06Z","timestamp":1788998106012,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ivonescimab (AK112) is a first\u2010in\u2010class bispecific antibody that simultaneously targets programmed death\u20101 (PD\u20101) and vascular endothelial growth factor (VEGF) with cooperative binding. We report the safety, pharmacokinetics (PK), and pharmacodynamics (PD) profiles of ivonescimab in patients suffered from advanced solid tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A multicenter, open\u2010label, dose\u2010escalation, phase I study was conducted in five hospitals in China. Ivonescimab was used as a monotherapy. The dose of ivonescimab intravenously administered was 3, 5, 10, 20, and 30\u2009mg\/kg every 2\u2009weeks (Q2W), and 10 and 20\u2009mg\/kg every 3\u2009weeks (Q3W). Safety, PK, and PD of ivonescimab were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 59 patients treated in the study. Only one dose\u2010limiting toxicity (DLT) occurred in 1 out of 9 patients in the 10\u2009mg\/kg Q2W cohort, indicating that no maximum tolerated dose was reached. Among the participants, 53 patients (89.8%) experienced treatment\u2010related adverse events (TRAEs), with the most common being proteinuria (33.9%), aspartate aminotransferase elevation (27.1%), white blood cell count decrease (22.0%), alanine aminotransferase elevation (20.3%), and anemia (20.3%). Fourteen patients (23.7%) had \u2265\u2009Grade 3 TRAEs, and 7 patients (11.9%) experienced serious TRAEs. Notably, there were no reported deaths associated with the TRAEs, and no dose\u2010dependent increase in adverse events was observed. The half\u2010life of ivonescimab ranged from 5.0 to 7.3\u2009days following single\u2010dose administration across all dose levels. The serum concentrations of ivonescimab increased with escalating doses in an approximately dose\u2010proportional manner. Following multiple doses, the accumulation ratio ranged from 1.1 to 1.7, suggesting mild accumulation of ivonescimab. The steady state was achieved after 5 doses. Ivonescimab occupancy on PD\u20101 sustained over 80% across the treatment period. Serum VEGF level was rapidly down\u2010regulated after each administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In patients with advanced solid tumors, ivonescimab monotherapy was well\u2010tolerated and demonstrated a linear PK characteristics. PD profiles showed the promising potential of ivonescimab for the management of advanced solid tumors.<\/jats:p><jats:p><jats:bold>Trial Registration:<\/jats:bold> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> (NCT04597541)<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70653","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T07:59:49Z","timestamp":1742716789000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Safety, Pharmacokinetics, and Pharmacodynamics Evaluation of Ivonescimab, a Novel Bispecific Antibody Targeting <scp>PD<\/scp>\u20101 and <scp>VEGF<\/scp>, in Chinese Patients With Advanced Solid Tumors"],"prefix":"10.1002","volume":"14","author":[{"given":"Fenghua","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Cancer Prevention Center Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Prevention Center Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital, Zhejiang University School of Medicine  Zhejiang Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecology Hunan Cancer Hospital  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieer","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Gastric Medicine Zhejiang Cancer Hospital  Zhejiang Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhong","family":"Chen","sequence":"additional","affiliation":[{"name":"The Department of Head and Neck Radiation Zhejiang Cancer Hospital  Zhejiang Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suxia","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Henan Cancer Hospital  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6312-9299","authenticated-orcid":false,"given":"Huiyan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Prevention Center Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4623-3203","authenticated-orcid":false,"given":"Xufang","family":"Yu","sequence":"additional","affiliation":[{"name":"Akeso Biopharma, Inc.  Zhongshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benchao","family":"Chen","sequence":"additional","affiliation":[{"name":"Akeso Biopharma, Inc.  Zhongshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ma","sequence":"additional","affiliation":[{"name":"Akeso Biopharma, Inc.  Zhongshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9771-8534","authenticated-orcid":false,"given":"Ruihua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Prevention Center Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81683-9"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1059"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc909"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-669"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.3343"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.35.15_suppl.4505"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.36.6_suppl.578"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy283.082"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716948"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.36.15_suppl.4074"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.35.4_suppl.673"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140559"},{"issue":"2","key":"e_1_2_12_16_1","first-page":"521","article-title":"521 AK112, a Tetravalent Bispecific Antibody Targeting PD\u20101 and VEGF, Enhances Binding Avidity and Functional Activities and Elicits Potent Anti\u2010Tumor Efficacy in Pre\u2010Clinical Studies","volume":"10","author":"Zhong T.","year":"2022","journal-title":"Journal for Immunotherapy of Cancer"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-008037"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102106"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2023.10.014"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.10613"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.030"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1586\/era.12.13"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.51"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000314980"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.70653","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:19:19Z","timestamp":1748348359000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.70653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/cam4.70653"],"URL":"https:\/\/doi.org\/10.1002\/cam4.70653","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"2024-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70653"}}