Phase 1/2 Trial of Seclidemstat in Ewing and FET-Rearranged Sarcomas Pauses Enrollment

New patient enrollment for a phase 1/2 trial (NCT03600649) assessing seclidemstat (SP-2577) as treatment for relapsed or refractory Ewing and FET-rearranged sarcomas has voluntarily paused enrollment after an unexpected death of a patient with a metastatic FET-rearranged sarcoma, according to a recent press release from Salarius Pharmaceuticals.¹

The death was identified as a suspected unexpected serious adverse reaction (SUSAR). Patients who have been actively receiving seclidemstat may resume treatment following a review of the SUSAR and available information by an independent safety review committee, as well as after consulting with their physician. Furthermore, drug developer Salarius intends on collaborating with the FDA to assess available data to expedite restarting enrollment. Interim trial results are still planned for release later this year.

“Patient safety is our primary concern, and this is reflected in the design of our clinical trial protocol, which automatically paused enrollment based upon this SUSAR,” David Arthur, chief executive officer at Salarius, said in the press release. “Unfortunately, pauses to enrollment occur in early-stage drug development, but these pauses allow time to understand new data and adjust clinical protocols and development plans as needed. We plan to restart enrollment as soon as possible.”

This single agent, non-randomized trial will evaluate LDS1 inhibitor seclidemstatin a population of patients with Ewing sarcoma, myxoid liposarcoma, and other sarcomas with comparable chromosomal translocations to Ewing sarcoma. Overall, the trial has an estimated enrollment of 50 patients across 3 arms, the first of which includes patients with myxoid liposarcoma receiving a twice-daily administration of oral seclidemstat. The second arm includes patients with sarcomas harboring FET-family translocations such as desmoplastic small round cell tumors who will receive a twice-daily administration of oral seclidemstat. The third study arm will include approximately 30 patients with Ewing sarcoma and compare seclidemstat with topotecan and cyclophosphamide. Cyclophosphamide will be administered at a dose of 250 mg/m2 and 0.75 mg/m2 of topotecan both taken on days 1 to 5 every 21-day cycle.

The primary trial end point is safety and tolerability of seclidemstat monotherapy and in combination with topotecan and cyclophosphamide. Secondary end points include the maximum tolerated dose of seclidemstat, pharmacokinetics, and anti-tumor activity per RECIST v 1.1 criteria.

Patients at least 12 years or older and 40 kg or more in weight are eligible to enroll on the trial. A Karnofsky performance status of at least 70% is necessary for patients older than 16 years or a Lansky performance status of at least 70% for those under 16 years. Additional inclusion criteria for all patient arms include a life expectancy greater than 4 months, a willingness to provide tumor biopsies during screening and while on treatment, normal organ and marrow function, and the ability to understand and willingness to sign a written informed consent document.

Seclidemstat was granted fast track designation for Ewing sarcoma by the FDA in December 2019.² The LDS1 inhibitor has also received orphan drug designation and rare pediatric disease designation from the FDA.

References

1. Salarius Pharmaceuticals announces pause in new patient enrollment in its phase 1/2 trial of seclidemstat in Ewing sarcoma and FET-rearranged sarcomas. News release. Salarius Pharmaceuticals, Inc. October 18, 2022. Accessed October 20, 2022. https://yhoo.it/3yWXhie
2. Salarius Pharmaceuticals receives FDA fast track designation for lead drug candidate, seclidemstat, in relapsed or refractory Ewing sarcoma. News release. Salarius Pharmaceuticals, Inc. December 16, 2019. Accessed October 20, 2022. https://bit.ly/3TA6xkb