Dataset Information

Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies.

ABSTRACT:

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.

SUBMITTER: Hollebecque A

PROVIDER: S-EPMC9540525 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies.

Hollebecque Antoine A Salvagni Stefania S Plummer Ruth R Niccoli Patricia P Capdevila Jaume J Curigliano Giuseppe G Moreno Victor V de Braud Filippo F de Villambrosia Sonia Gonzalez SG Martin-Romano Patricia P Baudin Eric E Arias Marina M de Alvaro Juan J Parra-Palau Josep L JL Sánchez-Pérez Tania T Aronchik Ida I Filvaroff Ellen H EH Lamba Manisha M Nikolova Zariana Z de Bono Johann S JS

Cancer 20220623 17

<h4>Background</h4>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.<h4>Methods</h4>CC-90011-ST-001 (ClincalTrials.gov identifier NCT02875223; Eudract number 2015-00 ...[more]

PMID: 35737639

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Dataset Information

Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies.

Background

Methods

Results

Conclusions

Publications

Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies.

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