On February 17, 2021 Salarius Pharmaceuticals, Inc. (Nasdaq: SLRX), a clinical-stage biopharmaceutical company developing potential new medicines for patients with pediatric cancers, solid tumors, and other cancers, reported that it has completed the dose-escalation stage and established the recommended Phase 2 dose (RP2D) for its ongoing Phase 1/2 clinical trial in relapsed/refractory (R/R) Ewing sarcoma (Press release, Salarius Pharmaceuticals, FEB 17, 2021, View Source [SID1234575184]).
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The Phase 1/2 clinical trial of seclidemstat in patients with Ewing sarcoma was designed as an open-label, multi-center, dose-finding study. The primary objectives of the study were to determine the safety and tolerability of seclidemstat. Secondary objectives were to assess the maximum-tolerated dose (MTD), the RP2D, preliminary anti-tumor activity, pharmacokinetics (PK), and pharmacodynamics.
Data from patients treated in the dose-escalation portion of the trial demonstrated seclidemstat had a manageable safety profile. The RP2D for the expansion stage has been established and, importantly, PK data from the dose-escalation portion of the trial indicated that treatment at the RP2D achieved plasma concentrations above levels where seclidemstat demonstrated activity in preclinical studies. Salarius is preparing to submit the full findings from the dose-escalation trial, including details on safety, dosing, and initial efficacy signals, for presentation at an upcoming medical conference. Conference embargo rules prevent additional disclosures at this time.
"The completion of dose escalation in Ewing sarcoma patients and establishment of the RP2D represent important milestones in our clinical development of seclidemstat," stated David Arthur, President and CEO of Salarius Pharmaceuticals. "We are encouraged by data from the dose-escalation phase and look forward to continuing development of seclidemstat for difficult to treat cancers."
Salarius is evaluating its lead drug candidate, seclidemstat, in patients with R/R Ewing sarcoma, a rare and deadly pediatric bone and soft tissue cancer and in a Phase 1/2 trial enrolling patients with Advanced Solid Tumors (AST). Seclidemstat is a novel, oral reversible inhibitor of the lysine-specific histone demethylase 1 enzyme (LSD1), an enzyme that has been shown to play a key role in the development and progression of certain cancers.
As previously reported, a refractory Ewing sarcoma patient treated with single-agent seclidemstat for six cycles (a cycle is 28 days), demonstrated a reduction in prospectively defined target lesions starting at end of cycle 2 with further target lesion tumor shrinkage through end of cycle 4 and cycle 6 (over 75% tumor shrinkage). The appearance of new non-target lesion at the end of cycle 2 resulted in classification of progressive disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Salarius believes this data demonstrates preliminary drug activity in a patient with refractory Ewing sarcoma. Additional data from the dose-escalation portion of the Ewing sarcoma trial has demonstrated further evidence of drug activity, which Salarius hopes to expand upon during the upcoming dose-expansion portion of the trial by treating R/R Ewing sarcoma patients with seclidemstat.
In addition to treating R/R Ewing sarcoma patients, the expansion portion of the Phase 1/2 trial will enroll patients with additional select sarcomas that share a similar biology to Ewing sarcoma. Fusions of similar oncogenes to those that are translocated in Ewing sarcoma occur in tumors, such as myxoid liposarcoma, desmoplastic small round cell tumors, and others known as Ewing-related sarcomas or FET-translocated sarcomas. The decision to include Ewing-related sarcoma patients was supported by preclinical data and encouraging clinical data in Salarius’ AST trial. Of the small subset of Ewing-related sarcoma patients with progressive disease that enrolled in the AST trial, all patients demonstrated preliminary evidence of seclidemstat drug activity at levels below the RP2D. Encouragingly, in this subset of seclidemstat treated patients, the median time to progression was above the benchmarks established for single-agent activity in the advanced, relapsed soft tissue sarcoma setting. Ewing-related sarcoma patients will continue to be treated with single-agent seclidemstat to generate more safety and early efficacy activity in this patient population. Safety and efficacy results from the AST trial are planned for presentation at an upcoming medical conference. Conference embargo rules prevent further disclosure at this time.
This study will continue to evaluate safety and antitumor activity with data readouts expected towards the end of this year and early next year.
Mr. Arthur concluded, "We are encouraged by the preliminary results from the Ewing sarcoma trial and the Advanced Solid Tumor trial that have demonstrated antitumor activity in patient populations with advanced disease. Based on the totality of the data accumulated thus far, we are optimistic about the potential of seclidemstat in multiple cancers."