Abstract CT109: A Phase I dose escalation and expansion study of seclidemstat (SP-2577) a first-in class reversible LSD1 inhibitor for patients with relapsed or refractory Ewing sarcoma
Abstract
Introduction: Ewing sarcoma is an aggressive pediatric and young adult bone tumor dependent almost exclusively on the EWS/ETS fusion protein family for transcriptional activity. EWS/FLI is the most common fusion resulting in the repression of vital tumor suppressor genes by the activity of lysine-specific histone demethylase 1 (LSD1). Seclidemstat (SP-2577) is a first in class, orally bioavailable, small molecule with reversible and noncompetitive selective inhibition of LSD1 at low nanomolar concentrations (IC50: 25-50 nM). Seclidemstat has demonstrated disruption of global transcriptional function of EWS/ETS fusions and impairs multiple EWS/ETS-associated oncogenic phenotypes in xenograft models of Ewing sarcoma. This Phase I study aims primarily to assess the safety and tolerability of seclidemstat and to secondarily characterize the pharmacokinetics (PK), food effects, and preliminary anti-tumor activity via RECIST 1.1. Exploratory objectives include using circulating tumor cells, cell-free DNA, and hemoglobin F as pharmacodynamic markers of response. Methods: This multi-center phase I study (NCT03600649) is open-label and non-randomized and utilizes an accelerated dose escalation phase followed by a conventional 3+3 design to determine the maximum tolerated dose (MTD). Initially, one subject per dose cohort will be recruited in the accelerated dose escalation phase until the first instance of grade 2 or greater drug related toxicity or dose limiting toxicity (DLT).…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 20 participants or records.
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