Trial of Seclidemstat in Ewing and FET-Rearranged Sarcomas Pauses Due to Safety Concern

A suspected unexpected serious adverse reaction to seclidemstat led the developer to pause a phase 1/2 evaluating the agent in patients with Ewing and FET-rearranged sarcoma.

A voluntary pause has been placed on a phase 1/2 trial that is evaluating treatment with seclidemstat in patients with Ewing sarcoma and FET-rearranged sarcoma, according to an announcement by the developer, Salarius Pharmaceuticals, Inc.

A patient enrolled in the study with metastatic FET-rearranged sarcoma died after developing a suspected unexpected serious adverse reaction (SUSAR) to seclidemstat. The occurrence of the SUSAR is being investigated by an independent safety review committee within the company. Other patients in the study who started treatment with seclidemstat are permitted to continue treatment during the pause.

“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,” said David Arthur, chief executive officer of Salarius, 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.”

The study of seclidemstat for the treatment of Ewing sarcoma and FET-rearranged sarcoma is a single-agent, non-randomized, open-label expansion study (NCT03600649). The study includes 3 treatment arms compiled of patients with either myxoid liposarcoma, sarcomas with FET-family translocations, including demoplastic small round cell tumors, and Ewing sarcoma. In the myxoid liposarcoma and FET-rearrangement arms, patients are treated with single-agent seclidemstat twice daily. In the Ewing sarcoma arm, patients are treated with twice daily seclidemstat in combination with cyclophosphamide 250 mg/m2 per day on days 1-5 of a 21-day cycle and topotecan 0.75 mg/m2 per day on days 1-5 of a 21-day cycle.

The primary end point of the study is the safety and tolerability of seclidemstat. The secondary end points include determining the maximum-tolerated dose of the agent, pharmacokinetics, and anti-tumor activity as measured by RECIST v1.1.

Once the pause is lifted from the trial, the study will continue recruiting eligible patients at 17 locations in the United States. Eligible patients are those aged 12 years or older with a weight of at least 40 kg. Patients are required to have a Karnofsky score of ≥ 70% if they are 16 years or age and older or a Karnofsky score 70% if they are under the age of 16 years. Patients must also have a life expectancy of greater than 4 months based on the opinion of the study investigator and have adequate organ and marrow function. Willingness to undergo biopsies and document consent are also requirements for study enrollment.

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. October 18, 2022. Accessed October 20, 2022. https://bit.ly/3F65unU

2. 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 20, 2022. https://clinicaltrials.gov/ct2/show/NCT03600649?term=Seclidemstat&draw=2&rank=2