{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:25:47Z","timestamp":1792772747714,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"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":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fanastomig (also known as EMB\u201002)\u00a0is a bispecific antibody targeting programmed cell death protein\u20101(PD\u20101) and lymphocyte activation gene\u20103 (LAG\u20103), developed for the treatment of advanced solid tumors. A first\u2010in\u2010human (FIH) Phase I study (NCT04618393) evaluated safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and clinical efficacy of Fanastomig in patients with advanced solid tumors. To determine the recommended Phase II dose (RP2D), population pharmacokinetics (PopPK), and exposure and response analysis (E\u2010R) were conducted. The PopPK model, demonstrating good performance, showed no clinically meaningful relationship between areas under the concentration\u2013time curve (AUC) or maximum concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ) of Fanastomig and selected covariates of interest. A nonlinear\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    model was fitted to Fanastomig PD\u20101 receptor occupancy (RO) in the peripheral blood compartment. The estimated half\u2010maximal effective concentration (EC\n                    <jats:sub>50<\/jats:sub>\n                    ) was 0.084 \u03bcg\/mL (95% confidence interval [CI]: 0.0369\u20130.131). Assuming a threefold lower exposure in tumor tissue compared to that in serum, a target trough concentration of Fanastomig at\n                    <jats:italic>~<\/jats:italic>\n                    2.27\u2009\u03bcg\/mL would be needed for 90% PD\u20101 RO in the tumor. Modeling and simulation indicated that a weekly dosing (QW) of 360\u2009mg would achieve full peripheral blood RO in approximately 90% of patients. The incidence of anti\u2010drug antibodies (ADAs) for Fanastomig was high (95.7%, 44\/46), with a negative correlation between the ADA titer and dose levels; meanwhile, ADA minimally impacted PK exposure and efficacy. An inverse trend was observed between anaphylaxis and PK exposure. Fanastomig was well tolerated and had acceptable safety profiles up to 900\u2009mg QW. Based on these findings, two dosing regimens have been selected for further clinical development.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    identifier: NCT04618393\n                  <\/jats:p>","DOI":"10.1002\/psp4.70011","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T18:16:01Z","timestamp":1741716961000},"page":"975-986","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Using Pharmacokinetic and Pharmacodynamic Analysis to Optimize the Dosing Regimens of Fanastomig (\n                    <scp>EMB<\/scp>\n                    \u201002) in Patients With Advanced Solid Tumors"],"prefix":"10.1002","volume":"14","author":[{"given":"Chengjun","family":"Jiang","sequence":"first","affiliation":[{"name":"Hanghai EpimAb Biotherapeutics Co., Ltd Shanghai EpimAb Biotherapeutics  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Ren","sequence":"additional","affiliation":[{"name":"Hanghai EpimAb Biotherapeutics Co., Ltd Shanghai EpimAb Biotherapeutics  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hanghai EpimAb Biotherapeutics Co., Ltd Shanghai EpimAb Biotherapeutics  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyang","family":"Lu","sequence":"additional","affiliation":[{"name":"Hanghai EpimAb Biotherapeutics Co., Ltd Shanghai EpimAb Biotherapeutics  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Hanghai EpimAb Biotherapeutics Co., Ltd Shanghai EpimAb Biotherapeutics  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[{"name":"Hanghai EpimAb Biotherapeutics Co., Ltd Shanghai EpimAb Biotherapeutics  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hanghai EpimAb Biotherapeutics Co., Ltd Shanghai EpimAb Biotherapeutics  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1007\/s00228-020-02924-x","article-title":"First\u2010In\u2010Human Dose: Current Status Review for Better 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L.","year":"2019","journal-title":"JAMA Oncology"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s40425-016-0177-2","article-title":"Nivolumab Dose Selection: Challenges, Opportunities, and Lessons Learned for Cancer Immunotherapy","volume":"4","author":"Agrawal S.","year":"2016","journal-title":"Journal for Immunotherapy of Cancer"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/s41416-018-0100-3","article-title":"Safety, Anti\u2010Tumour Activity, and Pharmacokinetics of Fixed\u2010Dose SHR\u20101210, an Anti\u2010PD\u20101 Antibody in Advanced Solid Tumours: A Dose\u2010Escalation, Phase 1 Study","volume":"119","author":"Mo H.","year":"2018","journal-title":"British Journal of Cancer"},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1056\/NEJMoa1200694","article-title":"Safety and Activity of Anti\u2013PD\u2010L1 Antibody in Patients With Advanced Cancer","volume":"366","author":"Brahmer J. 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