Salarius Pauses Phase 1/2 Trial Investigating Seclidemstat in Ewing Sarcoma and FET-Rearranged Sarcomas Following Death

Salarius Pharmaceuticals has voluntarily paused enrollment of new patients into a phase 1/2 trial (NCT03600649) investigating seclidemstat (SP-2577) in patients with Ewing sarcoma, sarcomas with FET-family translocations, and myxoid liposarcoma due to the death of a patient.¹

The death of the patient with metastatic FET-rearranged sarcoma has been classified as a suspected unexpected serious adverse reaction (SUSAR). Salarius has submitted details to the FDA and aims to understand how to proceed and restart enrollment as soon as possible.

Following a review by an independent safety review committee for the clinical trial, patients currently receiving seclidemstat may continue treatment after consulting with their physician.

“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 of Salarius, stated in a 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.”

In December 2019, the FDA granted fast track designation to seclidemstat for the treatment of relapsed/refractory patients with Ewing sarcoma.²

The phase 1/2 trial enrolled patients at least 12 years of age and weighing at least 40 kg who had Ewing sarcoma, myxoid liposarcoma, or FET-translocated sarcoma.³ All patients were required to have a Karnofsky performance status of at least 70% for over those who were at least 16 years old or a Lansky performance status of at least 70% for those under 16 years old. Patients also needed to have a life expectancy of more than 4 months, plus adequate bone marrow and organ function.

Those with Ewing sarcoma were required to have a histologic confirmed diagnosis of Ewing sarcoma with a known EWSR1 translocation through local assessment that is relapsed or refractory after at least one prior course of therapy for Ewing sarcoma. Patients must have had no more than 2 lines of systemic treatment for Ewing sarcoma, and no prior therapy with the combination regimen of topotecan and cyclophosphamide was permitted. Prior cyclophosphamide is allowed if not combined with topotecan.

Patients enrolled in the myxoid liposarcoma cohort or the FET-translocated sarcoma cohort needed to have a histologic confirmed diagnosis of one of the sarcomas that share similar known chromosomal translocations to Ewing sarcoma. Patients needed to be relapsed or refractory and not amenable to surgery at time of enrollment. Between 1 and 3 courses of prior systemic therapy for sarcoma was required.

Enrolled patients with Ewing sarcoma received a twice-daily administration of seclidemstat in combination with cyclophosphamide and topotecan. Those in the myxoid liposarcoma cohort or the FET-translocated sarcoma cohort were given a twice-daily administration of seclidemstat alone.

The primary end point of the trial is the safety and tolerability of treatment with seclidemstat. Establishing the maximum tolerated dose of seclidemstat, pharmacokinetics, and antitumor activity serve as secondary end points.

Despite the voluntary enrollment pause, Salarius plans to release interim clinical trial results later in 2022.

References

1. Salarius Pharmaceuticals announces pause in new patient enrollment in its phase 1/2 trial of seclidemstat in Ewing sarcoma and FET-rearranged sarcoma. News release. Salarius Pharmaceuticals. October 18, 2022. Accessed October 19, 2022. https://yhoo.it/3D7FZS0
2. Salarius Pharmaceuticals receives FDA fast track designation for lead drug candidate, seclidemstat, in relapsed or refractory Ewing sarcoma. News release. Salarius Pharmaceuticals. December 16, 2019. Accessed October 19, 2022. https://bit.ly/2LZ3AcD 
3. Clinical trial of SP-2577 (seclidemstat) in patients with relapsed or refractory Ewing or Ewing-related sarcomas. ClinicalTrials.gov. Updated August 25, 2022. Accessed October 19, 2022. https://clinicaltrials.gov/ct2/show/NCT03600649