Phase 1 Trial of the LSD1 Inhibitor Seclidemstat (SP 2577) With and Without Topotecan and Cyclophosphamide in Patients With Relapsed or Refractory Ewing Sarcoma and Select Sarcomas

• Age ≥ 12 years and weight ≥ 40 kg.

• Karnofsky ≥ 70% for over ≥ 16 years old and Lansky ≥ 70% for under 16 years old, equivalent to Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1.

• Life expectancy of greater than 4 months in investigator's opinion.

• Willingness to provide tumor biopsies during screening and while on treatment. Optional for patients \< 18 years of age and patients enrolled in the Ewing sarcoma combination treatment arm. Biopsies can be exempt if deemed by the investigator that the biopsy is not medically feasible for the patient or the patient is unfit for the procedure.

• Normal organ and marrow function as defined below:

‣ absolute neutrophil count (ANC) ≥ 1.5 x 109/L

⁃ platelets ≥ 100 x 109/L; no transfusion 7 days prior to labs

⁃ total bilirubin ≤ 1.5 x upper limit of normal (ULN) or, in patients with Gilbert syndrome, total bilirubin \> 1.5 x ULN as long as direct bilirubin is normal

⁃ AST and ALT ≤ 3 x ULN

⁃ creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above normal

• Ability to understand and the willingness to sign a written informed consent document.

∙ Additional Inclusion Criteria for Ewing Sarcoma Combination Treatment Cohort

• Patients must have a histologic confirmed diagnosis of Ewing sarcoma with a known EWSR1 translocation through local assessment that is relapsed or refractory and must have received at least one prior course of therapy for Ewing sarcoma. For the purposes of this study, refractory disease is defined as metastatic or unresectable disease that has either progressed or is stable at completion of planned therapy.

• Patients must have had no more than 2 lines/courses of systemic treatment for Ewing sarcoma

• No prior therapy with the combination regimen of topotecan and cyclophosphamide. Prior cyclophosphamide is allowed if not combined with topotecan.

• Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

∙ Additional Inclusion Criteria for Single Agent Myxoid Liposarcoma Cohort and for Single Agent FET-Translocated Sarcomas

• Patients must have a histologic confirmed diagnosis of one of the following sarcomas that share similar known chromosomal translocations to Ewing sarcoma (per local assessment) and are relapsed or refractory and not amenable to surgery at time of enrollment.

• Patients must have received at least one prior course of systemic therapy but no more than 3 courses of systemic therapy for sarcoma.

• Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1