{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:55:20Z","timestamp":1792652120716,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008021","name":"Bristol-Myers Squibb Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>CC\u201090011 is an oral, potent, selective, reversible inhibitor of lysine\u2010specific demethylase 1 (LSD1) that was well tolerated, with encouraging activity in patients who had advanced solid tumors or relapsed\/refractory marginal zone lymphoma. The authors present long\u2010term safety and efficacy and novel pharmacodynamic and pharmacokinetic data from the first\u2010in\u2010human study of CC\u201090011.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CC\u201090011\u2010ST\u2010001 (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clincaltrials.gov\">ClincalTrials.gov<\/jats:ext-link> identifier NCT02875223; Eudract number 2015\u2013005243\u201013) is a phase 1, multicenter study in which patients received CC\u201090011 once per week in 28\u2010day\u2009cycles. The objectives were to determine the safety, maximum tolerated dose, and\/or recommended phase 2 dose (primary) and to evaluate preliminary efficacy and pharmacokinetics (secondary).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010nine patients were enrolled, including 50 in the dose\u2010escalation arm and 19 in the dose\u2010expansion arm. Thrombocytopenia was the most common treatment\u2010related adverse event and was successfully managed with dose modifications. Clinical activity with prolonged, durable responses were observed, particularly in patients who had neuroendocrine neoplasms. In the dose\u2010escalation arm, one patient with relapsed\/refractory marginal zone lymphoma achieved a complete response (ongoing in cycle 58). In the dose\u2010expansion arm, three patients with neuroendocrine neoplasms had stable disease after nine or more cycles, including one patient who was in cycle 46 of ongoing treatment. CC\u201090011 decreased levels of secreted neuroendocrine peptides chromogranin A, progastrin\u2010releasing peptide, and RNA expression of the blood pharmacodynamic marker <jats:italic>monocyte\u2010to\u2010macrophage differentiation\u2013associated<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The safety profile of CC\u201090011 suggested that its reversible mechanism of action may provide an advantage over other irreversible LSD1 inhibitors. The favorable tolerability profile, clinical activity, durable responses, and once\u2010per\u2010week dosing support further exploration of CC\u201090011 as monotherapy and in combination with other treatments for patients with advanced solid tumors and other malignancies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.34366","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T13:13:27Z","timestamp":1655990007000},"page":"3185-3195","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Clinical activity of <scp>CC\u201090011<\/scp>, an oral, potent, and reversible <scp>LSD1<\/scp> inhibitor, in advanced malignancies"],"prefix":"10.1002","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2869-7551","authenticated-orcid":false,"given":"Antoine","family":"Hollebecque","sequence":"first","affiliation":[{"name":"Gustave Roussy D\u00e9partement d'innovation th\u00e9rapeutique et essais pr\u00e9coces  Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Salvagni","sequence":"additional","affiliation":[{"name":"S. Orsola Polyclinic Malpighi University Hospital  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Plummer","sequence":"additional","affiliation":[{"name":"Clinical and Translational Research Institute Northern Newcastle University  Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Niccoli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology ENETS Center of Excellence IPC NET Center Institut Paoli\u2010Calmettes  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8017-9941","authenticated-orcid":false,"given":"Jaume","family":"Capdevila","sequence":"additional","affiliation":[{"name":"Vall d'Hebron Institute of Oncology Vall d'Hebron University Hospital  IOB\u2010Teknon Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1781-2518","authenticated-orcid":false,"given":"Giuseppe","family":"Curigliano","sequence":"additional","affiliation":[{"name":"European Institute of Oncology, IRCCS, University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6099-4236","authenticated-orcid":false,"given":"Victor","family":"Moreno","sequence":"additional","affiliation":[{"name":"START Center for Cancer Care Jimenez Diaz University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"de Braud","sequence":"additional","affiliation":[{"name":"National Cancer Institute  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia Gonzalez","family":"de Villambrosia","sequence":"additional","affiliation":[{"name":"Department of Hematology Hospital Universitario Marqu\u00e9s de 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