Clinical activity of CC‐90011 , an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies
| العنوان: | Clinical activity of |
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| المؤلفون: | Antoine Hollebecque, Stefania Salvagni, Ruth Plummer, Patricia Niccoli, Jaume Capdevila, Giuseppe Curigliano, Victor Moreno, Filippo de Braud, Sonia Gonzalez de Villambrosia, Patricia Martin‐Romano, Eric Baudin, Marina Arias, Juan de Alvaro, Josep L. Parra‐Palau, Tania Sánchez‐Pérez, Ida Aronchik, Ellen H. Filvaroff, Manisha Lamba, Zariana Nikolova, Johann S. de Bono |
| المساهمون: | Institut Català de la Salut, [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, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | enzimas y coenzimas::enzimas::oxidorreductasas::oxidorreductasas que actúan sobre donantes de grupos CH-NH::oxidorreductasas N-desmetilantes::histona desmetilasas [COMPUESTOS QUÍMICOS Y DROGAS], Histone Demethylases, Cancer Research, Maximum Tolerated Dose, Càncer - Tractament, Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-NH Group Donors::Oxidoreductases, N-Demethylating::Histone Demethylases [CHEMICALS AND DRUGS], Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, B-Cell, Marginal Zone [DISEASES], neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B de la zona marginal [ENFERMEDADES], Investigative Techniques::Toxicity Tests::Maximum Tolerated Dose [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Lymphoma, B-Cell, Marginal Zone, Posologia, Neoplasms [DISEASES], neoplasias [ENFERMEDADES], Oncology, Neoplasms, Medicaments - Eficàcia, técnicas de investigación::pruebas de toxicidad::dosis máxima tolerada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Humans, Organic Chemicals |
| الوصف: | Lysine-specific demethylase 1 (LSD1) inhibitor; Neuroendocrine tumor; Non-Hodgkin lymphoma Tumor neuroendocrino; Linfoma no Hodgkin; Inhibidores de desmetilasa-1 específica a lisina Tumor neuroendocrí; Limfoma no Hodgkin; Inhibidor de la desmetilasa-1 específica a la lisina Background 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. This study was supported by Bristol Myers Squibb, Princeton, New Jersey, USA. Writing and editorial assistance was provided by Bio Connections, LLC, funded by Bristol Myers Squibb. |
| وصف الملف: | application/pdf |
| تدمد: | 1097-0142 0008-543X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2e349df9c191fe0587311b16411e9875Test https://doi.org/10.1002/cncr.34366Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2e349df9c191fe0587311b16411e9875 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970142 0008543X |
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