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This study aimed to evaluate the safety, pharmacokinetics (PK), and antitumor activity of escalating doses of SYHA1813 in patients with recurrent high-grade gliomas (HGGs) or advanced solid tumors. This study adopted a combination of accelerated titration and a 3\u2009+\u20093 design for dose escalation, with a starting dose of 5\u00a0mg once daily. The dose escalation continued at successive dose levels until the maximum tolerated dose (MTD) was determined. A total of 14 patients were enrolled and treated, including 13 with WHO grade III or IV gliomas and 1 with colorectal cancer. Two patients experienced dose-limiting toxicities (grade 4 hypertension and grade 3 mucositis oral) at 30\u00a0mg SYHA1813. The MTD was defined as 15\u00a0mg once daily. Hypertension (n\u2009=\u20096, 42.9%) was the most frequent treatment-related adverse event. Among evaluable patients (n\u2009=\u200910), 2 (20%) patients achieved partial response, and 7 (70%) had stable disease. The exposure increased with increasing doses within the studied dose range of 5 to 30\u00a0mg. Biomarker assessments demonstrated significant reductions in the levels of soluble VEGFR2 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u2009.0023) and increases in the levels of VEGFA (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u2009.0092) and placental growth factor (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u2009.0484). The toxicities of SYHA1813 were manageable, and encouraging antitumor efficacy was observed in patients with recurrent malignant glioma. This study is registered with the Chinese Clinical Trial Registry (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.chictr.org.cn\/index.aspx\">www.chictr.org.cn\/index.aspx<\/jats:ext-link>\n                    ; identifier ChiCTR2100045380).\n                  <\/jats:p>","DOI":"10.1007\/s10637-022-01325-4","type":"journal-article","created":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T16:09:04Z","timestamp":1678550944000},"page":"296-305","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A phase I dose-escalation study of SYHA1813, a VEGFR and CSF1R inhibitor, in patients with recurrent High-Grade Gliomas or Advanced Solid Tumors"],"prefix":"10.1007","volume":"41","author":[{"given":"Zhuang","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangzhi","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbo","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"1325_CR1","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/s0092-8674(00)80108-7","volume":"86","author":"D Hanahan","year":"1996","unstructured":"Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. 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The other authors have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The studies involving human participants were reviewed and approved by an institutional review board at each participating site. This study is registered at chictr.org.cn (trial registration ID: ChiCTR2100045380).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All patients provided written informed consent prior to the initiation of any study-related procedures.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors affirm that human research participants provided informed consent for the publication of the images in Supplementary Figures S4 and S5.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}]}}