CDK9 Inhibitor Earns FDA FTD in Relapsed/Refractory Acute Myeloid Leukemia

SLS009 received orphan drug designation from the FDA in relapsed/refractory AML in October 2023.

SLS009, a highly selective CDK9 inhibitor, has received FDA fast track designation for the treatment of relapsed/refractory acute myeloid leukemia (AML), according to a press release from SELLAS Life Sciences.¹

The agent is currently being assessed as part of a phase 2a study, in which 9 patients have been enrolled at the 45 mg safety dose level. Of these patients, 8 remain alive, and 6 are receiving ongoing treatment. Moreover, median overall survival has not been reached, and a significant antileukemic effect was observed in 87.5% of evaluable patients. The median follow-up for surviving patients ranges between 2 and 7 months.

The first patient who enrolled on the study experienced a complete response (CR) and is in their seventh month of survival with complete hematologic recovery.

“Receiving fast track designation for SLS009 for [relapsed/refractory] AML, following the recent orphan drug designation for the same indication, underscores the potential for SLS009 and highlights the critical unmet need for patients with AML who [have] a poor prognosis due to the progressive nature of the disease,” Angelos Stergiou, MD, ScD h.c., president and chief executive officer at SELLAS, said in the press release.¹ “The initial positive topline phase 2a data at the 45 mg [safety] dose level demonstrate that SLS009 in combination with venetoclax [Venclexta] and azacitidine [Vidaza; aza/ven] exhibits anti-leukemic effects with a favorable safety profile in [patients with] AML resistant to venetoclax combination therapies.”

In phase 1 of the study, single-agent SLS009 yielded a durable CR with no evidence of minimal residual disease in 1 patient who had previously progressed following azacitidine and venetoclax; the patient remains alive at 16 months after beginning treatment.

Investigators noted that there have been no notable safety issues in assessable patients, as well as no dose limiting toxicities.

The open-label, single arm, multicenter study was designed to assess the safety and efficacy of SLS009 at 2 doses levels—45 mg and 60 mg—and in combination with azacitidine and venetoclax. Those receiving the agent at 60 mg are being randomly assigned to get either a fixed dose once weekly or a fixed dose of 30 mg twice per week. Each cohort will range between 5 and 10 patients.

The study’s primary end points are safety and tolerability, composite CR rate, and duration of response, with other end points including event-free survival, overall survival, and pharmacokinetic/pharmacodynamic profiles.

It is expected that additional data from the 45 mg arm and initial findings from the 60 mg arm will read out in the first quarter of 2024, with additional findings from the 60 mg arm anticipated in the second quarter of 2024.

“SLS009 continues to emerge as a promising treatment for hematologic malignancies, and we are pleased by the FDA’s recognition of its potential by the grant of fast track and orphan drug designations for AML,” Stergiou concluded.1 “These designations position us to accelerate SLS009 clinical development with the goal of delivering this potentially groundbreaking treatment to [patients with] AML in need.”

SLS009 received orphan drug designation from the FDA in relapsed/refractory AML in October 2023.²

References

1. SELLAS Life Sciences receives FDA fast track designation for SLS009 for treatment of relapsed/refractory acute myeloid leukemia and provides updated data for phase 2a study of SLS009 in relapsed/refractory acute myeloid leukemia patients. News release. Sellas Life Sciences Group. January 9, 2023. Accessed January 9, 2023. https://bit.ly/48jO0QV
2. SELLAS receives FDA orphan drug designation for SLS009 for treatment of acute myeloid leukemia. News release. SELLAS Life Sciences Group. October 10, 2023. Accessed January 10, 2024. https://rb.gy/dj38w3