SLS009 Earns FDA Orphan Drug Designation in Acute Myeloid Leukemia
Data from a phase 1 study support the orphan drug designation for SLS009 as a treatment for patients with acute myeloid leukemia.
Investigators of an open-label phase 1/2a trial (NCT04588922) are evaluating the safety, tolerability, and efficacy of SLS009 in a dose escalation group including those with relapsed/refractory AML and in another group of those with relapsed/refractory lymphomas.
The FDA has granted orphan drug designation to the investigational CDK9 inhibitor SLS009 as a treatment for those with acute myeloid leukemia (AML), according to a press release from SELLAS Life Sciences Group, Inc.1
Supporting data for the orphan drug designation came from a phase 1 study (NCT04588922) in which treatment with SLS009 led to 77.3% bone marrow blast reduction. Additionally, investigators reported durable complete remission (CR) without minimal residual disease and desirable levels of MCL1 and MYC suppression in peripheral blood among 97% (n = 66/68) of evaluable patients.
Treatment with SLS009 produced no dose-limiting toxicities or high-grade non-hematologic toxicities, although there were some hematologic toxicities that were difficult to determine in those with hematologic malignancies. Investigators noted that these toxicities had limited duration and were reversible.
“We are honored to receive the [orphan drug designation] from the FDA. This designation underscores the potential of SLS009 to address a significant unmet medical need for patients with AML,” Angelos Stergiou, MD, ScD h.c., president and chief executive officer at SELLAS, said in the press release.1 “With the support of this [orphan drug designation], we look forward to accelerating SLS009 clinical development and bringing new hope to those [with] this devastating disease.”
Investigators of the open-label phase 1/2a trial are evaluating the safety, tolerability, and efficacy of SLS009 in a dose escalation group including those with relapsed/refractory AML and in another group of those with relapsed/refractory lymphomas. In the dose escalation portion, patients will receive SLS009 at escalating dose levels based on the Bayesian optimal interval design.
The study’s primary end points are dose-limiting toxicities and adverse effects. Secondary end points include pharmacokinetics, CR rate, duration of response, progression-free survival, and overall survival.
Patients 18 years and older with cytologically or histologically confirmed relapsed or refractory hematologic malignancies and adequate total bilirubin levels are able to enroll on the study. Additional eligibility criteria include having amylase levels no higher than 1.5 times the upper limit of normal and stable electrolytes and uric acid levels.
Those with bulky disease requiring cytoreductive surgery and symptomatic central nervous system (CNS) metastases or primary lymphoma including primary CNS lymphoma, leptomeningeal disease, or spinal cord compression are unable to enroll. Patients are also unsuitable for enrollment if they have severe cardiovascular disease within 6 months of entry, a concurrent malignancy within 5 years of entry, active hepatitis B or C virus infection, or receive concomitant medications that are strong CYP3A4 inhibitors within 7 days of the first dose.
In a previous readout of topline data from the relapsed/refractory lymphoma cohort of the trial, 14.7% (n = 5/34) achieved a clinical response following treatment with SLS009, which included a reduction in tumor burden of up to 62%.2 Investigators reported stable disease in 20.6%, yielding an overall disease control rate of 35.3%. Additionally, the clinical response rate was 36.4% (n = 4/11) in a subgroup of patients with peripheral T-cell lymphoma.
“The data demonstrate meaningful anti-tumor activity and clinical responses as a monotherapy. Based on its favorable therapeutic profile, SLS009 continues to emerge as a potential treatment for patients with hematologic malignancies who have exhausted available treatment options,” Stergiou said in a press release on data from the lymphoma cohort.2
References
- SELLAS receives FDA orphan drug designation for SLS009 for treatment of acute myeloid leukemia. News release. SELLAS Life Sciences Group, Inc. October 10, 2023. Accessed October 12, 2023. https://shorturl.at/apW04
- SELLAS announces positive topline data in lymphoma cohort from SLS009 phase 1 dose-escalation trial, supporting advancement to phase 2 clinical study; primary and secondary endpoints met. News release. SELLAS Life Sciences Group, Inc. September 21, 2023. Accessed October 12, 2023. https://bit.ly/3QdurTL
