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We enrolled 16 patients with relapsed\/refractory acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), chronic myelomonocytic leukemia (CMML), or myelodysplastic syndrome (MDS). A 3 + 3 dose escalation design was used with two planned dose levels (120 or 160\u00a0mg daily) and one de\u2010escalation level (80\u00a0mg daily). An additional 10 patients were treated on an expansion cohort. The recommended phase two dose of regorafenib was 160\u00a0mg daily, with no dose\u2010limiting toxicities. The best overall disease response by International Working Group criteria included one partial and stable disease in 11 patients. Tissue studies indicated no change in Ras\/mitogen\u2010activated protein kinase (MAPK) pathway activation in responders. Pharmacodynamic changes in plasma VEGF, PlGF, and sVEGFR2 were detected during treatment. Baseline proinflammatory and angiogenic cytokine levels were not associated with clinical response. Single\u2010agent regorafenib demonstrated an acceptable safety profile in relapsed\/refractory myeloid malignancy patients. Most patients achieved stable disease, with modest improvements in cell counts in some MDS patients. Biomarker studies were consistent with on\u2010target effects of regorafenib on angiogenesis. Future studies should investigate the role of regorafenib in combination therapy approaches.<\/jats:p>","DOI":"10.1002\/jha2.408","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T04:03:40Z","timestamp":1646625820000},"page":"434-442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A nonrandomized phase I and biomarker trial of regorafenib in advanced myeloid malignancies"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6421-0117","authenticated-orcid":false,"given":"Joan","family":"How","sequence":"first","affiliation":[{"name":"Division of Hematology Brigham and Women's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyang","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Data Sciences Dana\u2010Farber Cancer Institute  Boston Massachusetts 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