Clinical Trial of Seclidemstat for Ewing Sarcoma Adds Fox Chase Cancer Center to List of Treatment Sites

The Fox Chase Cancer Center at Temple University in Philadelphia, Pennsylvania has been added as an active trial site by Salarius Pharmaceuticals, Inc. for the ongoing trial (NCT03600649) of seclidemstat (SP-2577) for the treatment of relapsed or refractory Ewing sarcoma and advanced FET-rearranged sarcomas, according to a press release by the Fox Chase Cancer Center.

Seclidemstat is a lysine-specific histone demethylase 1 (LSD1)-inhibitor. This enzyme has been found to play a key role in the development and progression of several cancer types.

The open-label, non-randomized, parallel assignment study has an estimated enrollment of 50 patients and an estimated study completion date of December 2021. The primary end point of the study is the safety and tolerability of seclidemstat either as a single agent or in combination with topotecan and cyclophosphamide as measured by dose-limiting toxicities and adverse events (AEs). Secondary end points include the maximum tolerated dose as measured by dose-limiting toxicities, the pharmacokinetics of the agent, and anti-tumor activity as measured by RECIST 1.1 criteria based upon radiological assessments.

The study is composed of 3 arms. Patients in each arm will receive a twice-daily administration of oral seclidemstat. Arm 1 will enroll up to 30 patients with Ewing sarcoma. The study agent will be administered in combination with topotecan and cyclophosphamide, which is a commonly used second- and third-line chemotherapy regimen. The second arm will be made up of up to 15 patients with myxoid liposarcoma. Seclidemstat will be used as a single agent in this arm. Arm 3 will be made up of up to 15 patients with sarcomas with FET-family translocations, including desmoplastic small round cell tumors. Seclidemstat will also be used as a single agent in this arm.

“We are excited to be working with Salarius and look forward to exploring the potential of seclidemstat and its ability to inhibit the LSD1 enzyme,” stated Johnathan Whetstine, PhD, director, Cancer Epigenetics Institute, Fox Chase Cancer Center, in a press release. “Based on our extensive research into the epigenetic causes of cancer, we believe LSD1 inhibition holds great promise in the treatment of many cancers. We believe data from preclinical studies using Ewing sarcoma cell lines has demonstrated the molecule’s ability to hit two aspects of the enzyme simultaneously. This, added to clinical data showing drug activity across Ewing and other sarcomas, support the further exploration of seclidemstat in these high unmet need patient populations.”

In order to participate, patients must be at least 12 years of age and weigh at least 40kg. Additionally, patients must be Karnofsky ≥ 70% for over ≥ 16 years old and Lansky ≥ 70% for under 16-year-olds. This is equivalent to Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1. Patients must also have a life expectancy of greater than 4 months, have normal organ and marrow function, and be able to understand and provide informed written consent. Patients in the Ewing sarcoma combination treatment cohort must have confirmed Ewing sarcoma, have had no more than 2 lines of systemic treatment, no prior therapy with the combination of topotecan and cyclophosphamide, and measurable disease per RECIST v1.1. Patients in the other 2 cohorts must have a confirmed diagnosis of a sarcoma that shares a similar known chromosomal translocation to Ewing sarcoma, have had at least 1 prior line of therapy but not more than 3 courses of systemic therapy for sarcoma.

Patients who are receiving therapy with other anti-neoplastic or experimental agents have had prior therapy with LSD1-targeting agents, prior oral tyrosine kinase exposure, other systemic anti-cancer treatments, prior therapy with immunotherapy such as a checkpoint inhibitor, prior small port palliative radiotherapy within 14 days of cycles 1 day 1 or within 42 days of cycle 1 day 1 from definitive local control radiation, uncontrolled concurrent illness, clinically significant uncontrolled heart disease, or HIV patients on combination antiretroviral therapy are not eligible to participate.

In total, 9 centers are participating in the study across 7 states. Other states where centers are located include California, Florida, Massachusetts, New York, Ohio, and Texas.

_REFERENCE:

_{Salarius Pharmaceuticals adds Fox Chase Cancer Center to ongoing trial of seclidemstat as a treatment for Ewing sarcoma and FET-rearranged sarcomas. News release. Fox Chase Cancer Center. July 13, 2021. Accessed July 16, 2021. https://bit.ly/2UgSVBe.}