| Title: |
Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies. |
| Authors: |
Hollebecque, A; Salvagni, S; Plummer, R; Niccoli, P; Capdevila, J; Curigliano, G; Moreno, V; de Braud, F; de Villambrosia, SG; Martin-Romano, P; Baudin, E; Arias, M; de Alvaro, J; Parra-Palau, JL; Sánchez-Pérez, T; Aronchik, I; Filvaroff, EH; Lamba, M; Nikolova, Z; de Bono, JS |
| Contributors: |
De Bono, Johann |
| Publisher Information: |
WILEY |
| Publication Year: |
2025 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
CC-90011; epigenetic repression; lysine-specific demethylase 1 (LSD1) inhibitor; neuroendocrine tumor; non-Hodgkin lymphoma; pulrodemstat besilate; Histone Demethylases; Humans; Lymphoma; B-Cell; Marginal Zone; Maximum Tolerated Dose; Neoplasms; Organic Chemicals |
| Subject Geographic: |
United States |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print-Electronic; 3195; application/pdf |
| Language: |
English |
| ISSN: |
1097-0142; 0008-543X |
| Relation: |
Cancer, 2022, 128 (17), pp. 3185 - 3195; https://repository.icr.ac.uk/handle/internal/6706 |
| DOI: |
10.1002/cncr.34366 |
| Availability: |
https://doi.org/10.1002/cncr.34366; https://repository.icr.ac.uk/handle/internal/6706 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.815FCBEE |
| Database: |
BASE |