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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorHollebecque, Antoine
dc.contributor.authorSalvagni, Stefania
dc.contributor.authorPlummer, Ruth
dc.contributor.authorNiccoli, Patricia
dc.contributor.authorCapdevila Castillon, Jaume
dc.contributor.authorCurigliano, Giuseppe
dc.date.accessioned2022-09-12T09:40:12Z
dc.date.available2022-09-12T09:40:12Z
dc.date.issued2022-09-01
dc.identifier.citationHollebecque A, Salvagni S, Plummer R, Niccoli P, Capdevila J, Curigliano G, et al. Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies. Cancer. 2022 Sep 1;128(17):3185–95.
dc.identifier.issn1097-0142
dc.identifier.urihttp://hdl.handle.net/11351/8150
dc.descriptionLysine-specific demethylase 1 (LSD1) inhibitor; Neuroendocrine tumor; Non-Hodgkin lymphoma
dc.description.abstractBackground CC-90011 is an oral, potent, selective, reversible inhibitor of lysine-specific 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-term safety and efficacy and novel pharmacodynamic and pharmacokinetic data from the first-in-human study of CC-90011. Methods CC-90011-ST-001 (ClincalTrials.gov identifier NCT02875223; Eudract number 2015–005243-13) is a phase 1, multicenter study in which patients received CC-90011 once per week in 28-day cycles. 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). Results Sixty-nine patients were enrolled, including 50 in the dose-escalation arm and 19 in the dose-expansion arm. Thrombocytopenia was the most common treatment-related 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-escalation arm, one patient with relapsed/refractory marginal zone lymphoma achieved a complete response (ongoing in cycle 58). In the dose-expansion 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-90011 decreased levels of secreted neuroendocrine peptides chromogranin A, progastrin-releasing peptide, and RNA expression of the blood pharmacodynamic marker monocyte-to-macrophage differentiation–associated. Conclusions The safety profile of CC-90011 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-per-week dosing support further exploration of CC-90011 as monotherapy and in combination with other treatments for patients with advanced solid tumors and other malignancies.
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofseriesCancer;128(17)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectPosologia
dc.subjectCàncer - Tractament
dc.subjectMedicaments - Eficàcia
dc.subject.meshMaximum Tolerated Dose
dc.subject.meshNeoplasms
dc.subject.meshLymphoma, B-Cell, Marginal Zone
dc.subject.meshHistone Demethylases
dc.titleClinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1002/cncr.34366
dc.subject.decsdosis máxima tolerada
dc.subject.decsneoplasias
dc.subject.decslinfoma de células B de la zona marginal
dc.subject.decshistona desmetilasas
dc.relation.publishversionhttps://doi.org/10.1002/cncr.34366
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Hollebecque A] Gustave Roussy, Département d’innovation thérapeutique et essais précoces, Villejuif, France. [Salvagni S] S. Orsola Polyclinic, Malpighi University Hospital, Bologna, Italy. [Plummer R] Clinical and Translational Research Institute Northern, Newcastle University, Newcastle, UK. [Niccoli P] Department of Medical Oncology, ENETS Center of Excellence, IPC NET Center, Institut Paoli-Calmettes, Marseille, France. [Capdevila J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. IOB-Teknon, Barcelona, Spain. [Curigliano G] European Institute of Oncology, IRCCS, University of Milan, Milan, Italy
dc.identifier.pmid35737639
dc.identifier.wos000814787400001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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