MD Anderson Study Resumes With Seclidemstat/Azacitidine in MDS/CMML

Enrollment is set to resume for an investigator-initiated phase 1/2 trial (NCT04734990) evaluating seclidemstat plus azacitidine in patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The trial is led by investigators at The University of Texas MD Anderson Cancer Center.1

In July 2024, the FDA placed the study under a partial clinical hold following reports of a serious and unexpected adverse effect (AE). The university has since answered the FDA’s concerns, resulting in removal of the hold.

“Coming off partial clinical hold is welcome news for Salarius stakeholders and for patients with advanced MDS and CMML, and we are excited for [The University of Texas MD Anderson Cancer Center] to enroll additional patients and build upon seclidemstat’s growing clinical database,” David Arthur, president and chief executive officer of Salarius Pharmaceuticals, stated in a news release.

Seclidemstat is a novel, oral, reversible LSD1 inhibitor. In preclinical in vivo hematologic models LSD1 inhibition was found to reprogram cancer cell differentiation, lessen tumor burden, and extend animal survival.

Interim results from the phase 1/2 study, which were previously presented at the 2024 EHA Congress with a median follow-up of 18.9 months (95% CI, 0-48), demonstrated that treatment with the combination led to an objective response rate of 43% in patients with higher-risk MDS and CMML (n = 14) following prior therapy with hypomethylating agents (HMAs).2 Best responses included 1 complete response, 3 marrow complete responses, 1 marrow complete response plus hematological improvement, and 1 case of hematologic improvement.

Further results illustrated a median overall survival (OS) of 18.5 months (95% CI, 6.1-30.9), far surpassing the historical OS between approximately 4 and 6 months after progression on an HMA. Median event-free survival was 7.2 months (95% CI, 6.3-8.2).

Regarding safety, 15 of the 16 total enrolled patients were evaluable. One dose-limiting toxicity occurred in a patient who received 750 mg of seclidemstat twice daily. Per the study protocol, the cohort was expanded to 3 additional patients. At the time of the announcement Salarius Pharmaceuticals noted that the phase 1 dose-escalation portion of the study would evaluate up to 6 dose levels of seclidemstat, with 750 mg twice daily representing the fifth cohort and 900 mg twice daily representing the sixth. They also noted that the maximum tolerated dose, which will inform the recommended phase 2 dose, had not been reached.

To be eligible for enrollment in the ongoing phase 1/2 trial, patients must be at least 18 years of age and have received a diagnosis of MDS or CMML according to World Health Organization criteria.3 Notably, patients with MDS must have intermediate-1–, intermediate-2–, or high-risk disease according to the International Prognostic Scoring System. Patients with CMML need to have CMML-1, CMML-2, myeloproliferative CMML defined by a white blood cell of at least 13 x 109/L, or CMML-0 with high-risk molecular features, including mutations in ASXL1, SETBP1, RUNX1, NRAS, or TP53, or more than 3 mutations. Moreover, only patients who did not derive response to azacitidine, decitabine, guadecitabine, ASTX030, or ASTX727 after 6 cycles of therapy, or those who had disease relapse or progression after any number of cycles were eligible.

Other inclusion criteria consisted of an ECOG performance status of 0 to 2, adequate hepatic function with total bilirubin below 2 times the upper limit of normal (ULN), aspartate aminotransferase or alanine aminotransferase levels no higher than 3 times the ULN, and serum creatinine levels no higher than 1.5 times the ULN, or creatinine clearance of at least 50 mL/min for patients with creatinine levels above 1.5 times the ULN.

Eligible patients received oral seclidemstat once daily on day 1 of cycle 1 and twice daily on days 2 through 28 of cycle 1 and on days 1 through 28 thereafter. Patients also received intravenous azacitidine over a 10- to 40-minute span or subcutaneous administration on days 1 to 7. Treatment will continue in 28-day cycles in the absence of disease progression or unacceptable toxicity.

The primary end points of the study are ORR and the incidence of AEs. Secondary end points included OS, duration of response, leukemia-free survival, and relapse-free survival.

References

1. Salarius Pharmaceuticals announces patient enrollment to resume in investigator-initiated phase 1/2 clinical trial using seclidemstat with azacitidine to treat hematologic cancers. News release. Salarius Pharmaceuticals. February 3, 2025. Accessed February 7, 2025. https://salariuspharma.com/2025/02/03/salarius-pharmaceuticals-announces-patient-enrollment-to-resume-in-investigator-initiated-phase-1-2-clinical-trial-using-seclidemstat-with-azacitidine-to-treat-hematologic-cancers/
2. Clinical data on Salarius Pharmaceuticals’ seclidemstat in patients with MDS and CMML presented at the 2024 European Hematology Association Annual Meeting. News release. Salarius Pharmaceuticals. June 17, 2024. Accessed February 7, 2025. https://investors.salariuspharma.com/news-releases/news-release-details/clinical-data-salarius-pharmaceuticals-seclidemstat-patients-mds
3. Seclidemstat and azacitidine for the treatment of myelodysplastic syndrome or chronic myelomonocytic leukemia. ClinicalTrials.gov. Updated November 12, 2024. Accessed February 7, 2025. https://clinicaltrials.gov/study/NCT04734990