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This first-in-human, open-label, dose-escalation study to evaluate the safety, maximum tolerated dose (MTD), and preliminary efficacy of CWP291 enrolled 69 patients with hematologic malignancies (acute myeloid leukemia [AML], n = 64; myelodysplastic syndrome, n = 5) in 15 dose-escalation cohorts of 4 to 334 mg\/m2 using a modified 3+3 design and 1 dose-expansion cohort. CWP291 was administered IV daily for 7 days every 21 days. The most common treatment-emergent adverse events (TEAEs) were nausea (n = 44, 64%), vomiting (n = 32, 46%), diarrhea (n = 25, 36%), and infusion-related reactions (n = 20, 29%). Grade \u22653 TEAEs in &amp;gt;3 patients (5%) were pneumonia (n = 8, 12%); hypophosphatemia (n = 6, 8%); leukocytosis, nausea, cellulitis, sepsis, and hypokalemia (n = 5 each, 7% each); and hypertension (n = 4, 6%). Dose-limiting toxicities included nausea (n = 3) and abdominal pain, anaphylactic reaction, myalgia, and rash (n = 1, each); the MTD was defined at 257 mg\/m2. CWP232204, the active metabolite of CWP291, showed pharmacokinetic linearity on both days 1 and 7, and a terminal half-life of \u223c12 hours. Among 54 response-evaluable AML patients, there was one complete response at a dose of 153 mg\/m2 and one partial response at 198 mg\/m2; bone marrow blast percentage reduced from a median of 58.3% to 3.5% and 15.0% to 4.2%, respectively. Future studies will explore CWP291, with a mechanism of action aimed at eradication of earlier progenitors via Wnt pathway blockade, as combination therapy. This trial was registered at www.clinicaltrials.gov as #NCT01398462.<\/jats:p>","DOI":"10.1182\/bloodadvances.2019000757","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T22:45:24Z","timestamp":1589237124000},"page":"2032-2043","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":63,"title":["Phase 1 study of CWP232291 in patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome"],"prefix":"10.1182","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7060-1675","authenticated-orcid":false,"given":"Je-Hwan","family":"Lee","sequence":"first","affiliation":[{"name":"Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Faderl","sequence":"first","affiliation":[{"name":"Hackensack University Cancer Center, Hackensack, 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