{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:35:28Z","timestamp":1786980928073,"version":"build-2736575974"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Athenex Pharmaceuticals"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2022,8]]},"DOI":"10.1007\/s10637-022-01255-1","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T01:02:43Z","timestamp":1652749363000},"page":"773-781","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A phase Ib dose escalation study of oral monotherapy with KX2-391 in elderly patients with acute myeloid leukemia"],"prefix":"10.1007","volume":"40","author":[{"given":"Margaret T.","family":"Kasner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly B.","family":"Halloran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen K.","family":"Ritchie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald J.","family":"Fetterly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Kramer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Hangauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"issue":"9","key":"1255_CR1","doi-asserted-by":"publisher","first-page":"3323","DOI":"10.1182\/blood.V89.9.3323","volume":"89","author":"CP Leith","year":"1997","unstructured":"Leith CP, Kopecky KJ, Godwin J, McConnell T, Slovak ML, Chen IM, Head DR, Appelbaum FR, Willman CL (1997) Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study Blood 89(9):3323\u20133329. https:\/\/doi.org\/10.1182\/blood.V89.9.3323","journal-title":"A Southwest Oncology Group study Blood"},{"issue":"12","key":"1255_CR2","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.3324\/haematol.2008.000497","volume":"93","author":"MA Sekeres","year":"2008","unstructured":"Sekeres MA (2008) Treatment of older adults with acute myeloid leukemia: state of the art and current perspectives. Haematologica 93(12):1769\u20131772. https:\/\/doi.org\/10.3324\/haematol.2008.000497","journal-title":"Haematologica"},{"key":"1255_CR3","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1056\/NEJMoa2012971","volume":"7","author":"CD DiNardo","year":"2020","unstructured":"DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, D\u00f6hner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, H\u00e1jek R, Porkka K, Ill\u00e9s \u00c1, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW (2020) Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med 7:617\u2013629. https:\/\/doi.org\/10.1056\/NEJMoa2012971","journal-title":"N Engl J Med"},{"issue":"7","key":"1255_CR4","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1182\/blood.2019002140","volume":"135","author":"GJ Roboz","year":"2020","unstructured":"Roboz GJ, DiNardo CD, Stein EM, de Botton S, Mims AS, Prince GT, Altman JK, Arellano ML, Donnellan W, Erba HP, Mannis GN, Pollyea DA, Stein AS, Uy GL, Watts JM, Fathi AT, Kantarjian HM, Tallman MS, Choe S, Dai D, Fan B, Wang H, Zhang V, Yen KE, Kapsalis SM, Hickman D, Liu H, Agresta SV, Wu B, Attar EC, Stone RM (2020) Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood 135(7):463\u2013471. https:\/\/doi.org\/10.1182\/blood.2019002140","journal-title":"Blood"},{"key":"1255_CR5","doi-asserted-by":"publisher","unstructured":"Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, Stone RM, DeAngelo DJ, Levine RL, Flinn IW, Kantarjian HM, Collins R, Patel MR, Frankel AE, Stein A, Sekeres MA, Swords RT, Medeiros BC, Willekens C, Vyas P, Tosolini A, Xu Q, Knight RD, Yen KE, Agresta S, de Botton S, Tallman MS (2017) Enasidenib in mutant\u00a0IDH2\u00a0relapsed or refractory acute myeloid leukemia\u00a0Enasidenib in mutant\u00a0IDH2\u00a0relapsed or refractory acute myeloid leukemia.\u00a0Blood\u00a0130(6):722\u2013731.\u00a0https:\/\/doi.org\/10.1182\/blood-2017-04-779405","DOI":"10.1182\/blood-2017-04-779405"},{"issue":"18","key":"1255_CR6","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1056\/NEJMoa1902688","volume":"381","author":"AE Perl","year":"2019","unstructured":"Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ (2019) Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med 381(18):1728\u20131740. https:\/\/doi.org\/10.1056\/NEJMoa1902688","journal-title":"N Engl J Med"},{"key":"1255_CR7","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.blre.2019.04.005","volume":"36","author":"RM Shallis","year":"2019","unstructured":"Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM (2019) Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges. Blood Rev 36:70\u201387. https:\/\/doi.org\/10.1016\/j.blre.2019.04.005","journal-title":"Blood Rev"},{"key":"1255_CR8","unstructured":"Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (2021) SEER Cancer Statistics Review, 1975\u20132018, National Cancer Institute. Bethesda, MD,\u00a0https:\/\/seer.cancer.gov\/csr\/1975_2018\/, based on November 2020 SEER data submission, posted to the SEER web site, April 2021"},{"issue":"11","key":"1255_CR9","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.1182\/blood-2012-11-466425","volume":"122","author":"C Dos Santos","year":"2013","unstructured":"Dos Santos C, McDonald T, Ho YW, Liu H, Lin A, Forman SJ, Kuo YH, Bhatia R (2013) The Src and c-Kit kinase inhibitor dasatinib enhances p53-mediated targeting of human acute myeloid leukemia stem cells by chemotherapeutic agents. Blood 122(11):1900\u20131913. https:\/\/doi.org\/10.1182\/blood-2012-11-466425","journal-title":"Blood"},{"key":"1255_CR10","doi-asserted-by":"publisher","unstructured":"Saito Y, Yuki H, Kuratani M, Hashizume Y, Takagi S, Honma T, Tanaka A, Shirouzu M, Mikuni J, Handa N et al (2013) A pyrrolo-pyrimidine derivative targets human primary AML stem cells in vivo.\u00a0Sci Translational Med 5(181):181ra52. https:\/\/doi.org\/10.1126\/scitranslmed.3004387","DOI":"10.1126\/scitranslmed.3004387"},{"issue":"7","key":"1255_CR11","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.3390\/cancers12071996","volume":"12","author":"E Voisset","year":"2020","unstructured":"Voisset E, Brenet F, Lopez S, de Sepulveda P (2020) SRC-Family Kinases in Acute Myeloid Leukaemia and Mastocytosis. Cancers 12(7):1996. https:\/\/doi.org\/10.3390\/cancers12071996","journal-title":"Cancers"},{"issue":"11","key":"1255_CR12","doi-asserted-by":"publisher","first-page":"4704","DOI":"10.1021\/acs.jmedchem.8b00164","volume":"61","author":"MP Smolinski","year":"2018","unstructured":"Smolinski MP, Bu Y, Clements J, Gelman IH, Hegab T, Cutler DL, Fang JWS, Fetterly G, Kwan R, Barnett A, Lau JYN, Hangauer DG (2018) Discovery of Novel Dual Mechanism of Action Src Signaling and Tubulin Polymerization Inhibitors (KX2-391 and KX2-361). J Med Chem 61(11):4704\u20134719. https:\/\/doi.org\/10.1021\/acs.jmedchem.8b00164","journal-title":"J Med Chem"},{"issue":"4","key":"1255_CR13","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1007\/s00280-013-2079-z","volume":"71","author":"ES Antonarakis","year":"2013","unstructured":"Antonarakis ES, Heath EI, Posadas EM, Yu EY, Harrison MR, Bruce JY, Cho SY, Wilding GE, Fetterly GJ, Hangauer DG, Kwan MF, Dyster LM, Carducci MA (2013) A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol 71(4):883\u2013892. https:\/\/doi.org\/10.1007\/s00280-013-2079-z","journal-title":"Cancer Chemother Pharmacol"},{"issue":"4","key":"1255_CR14","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1007\/s10637-013-9929-8","volume":"31","author":"A Naing","year":"2013","unstructured":"Naing A, Cohen R, Dy GK, Hong DS, Dyster L, Hangauer DG, Kwan R, Fetterly G, Kurzrock R, Adjei AA (2013) A phase I trial of KX2-391, a novel non-ATP competitive substrate-pocket- directed SRC inhibitor, in patients with advanced malignancies. Invest New Drugs 31(4):967\u2013973. https:\/\/doi.org\/10.1007\/s10637-013-9929-8","journal-title":"Invest New Drugs"},{"issue":"7","key":"1255_CR15","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1007\/s10620-008-0519-0","volume":"54","author":"GM Lau","year":"2009","unstructured":"Lau GM, Yu GL, Gelman IH, Gutowski A, Hangauer D, Fang JW (2009) Expression of SRC and FAK in hepatocellular carcinoma and the effect of SRC inhibitors on hepatocellular carcinoma in vitro. Dig Dis Sci 54(7):1465\u20131474. https:\/\/doi.org\/10.1007\/s10620-008-0519-0","journal-title":"Dig Dis Sci"},{"issue":"24","key":"1255_CR16","doi-asserted-by":"publisher","first-page":"4642","DOI":"10.1200\/JCO.2003.04.036","volume":"21","author":"Cheson BD, Bennett JM, Kopecky KJ, B\u00fcchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, L\u00f6wenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia","year":"2003","unstructured":"Cheson BD, Bennett JM, Kopecky KJ, B\u00fcchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, L\u00f6wenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia (2003) Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J clinical oncol\u202f: official j Am Soc Clinical Oncol 21(24):4642\u20134649. https:\/\/doi.org\/10.1200\/JCO.2003.04.036","journal-title":"J clinical oncol : official j Am Soc Clinical Oncol"},{"issue":"3","key":"1255_CR17","doi-asserted-by":"publisher","first-page":"925","DOI":"10.2307\/2531693","volume":"45","author":"BE Storer","year":"1989","unstructured":"Storer BE (1989) Design and analysis of phase I clinical trials. Biometrics 45(3):925\u2013937","journal-title":"Biometrics"},{"key":"1255_CR18","unstructured":"Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (2008)\u00a0WHO classification of tumours of haematopoietic and lymphoid tissues\u00a0(Vol. 2, p. 439). S. H. Swerdlow (Ed.). Lyon, France: Int agency for resn cancer"}],"container-title":["Investigational New Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-022-01255-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10637-022-01255-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-022-01255-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T23:47:59Z","timestamp":1678492079000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10637-022-01255-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,17]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["1255"],"URL":"https:\/\/doi.org\/10.1007\/s10637-022-01255-1","relation":{},"ISSN":["0167-6997","1573-0646"],"issn-type":[{"value":"0167-6997","type":"print"},{"value":"1573-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,17]]},"assertion":[{"value":"28 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the principles of the World Medical Association Declaration of Helsinski, the International Council on Harmonization Good Clinical Practice Guideline, the US Code of Federal Regulations dealing with clinical studies, as well as the ethical standards of the participating institutional committees.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not Applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"Douglas Kramer and David G. Hangauer were employed at Athenex Pharmaceuticals. All remaining authors declare no financial or non-financial competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}