CDK9 Inhibitor SLS009 Displays Activity in Relapsed/Refractory AML

Angelos Stergiou, MD, ScD hc

A phase 2a study (NCT04588922) evaluating the CDK9 inhibitor SLS009 as treatment for patients with relapsed/refractory acute myeloid leukemia (AML) has completed enrollment and positive initial data have been shared.¹

At the May 25, 2024, data cutoff, efficacy-evaluable patients (n = 27) achieved an overall response rate (ORR) of 29.6% across all dose levels, and a maximum response rate of 50% was observed with the 30 mg twice weekly dosing regimen. The median overall survival (OS) was 5.4 months in patients who received the 45 mg once weekly dosing level.

“We are pleased to announce the completion of enrollment in the initial portion of our phase 2a trial representing a significant milestone in the development of SLS009 in AML,” Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS stated in a press release. “There has been a high level of enthusiasm from the clinical sites, trial investigators, and patients, reflecting the significant unmet need in the AML patient population previously treated with venetoclax [Venclexta]-based regimens.”

The open-label, single-arm, multicenter study enrolled patients with relapsed or refractory hematologic malignancies including AML, chronic lymphocytic leukemia, small lymphocytic lymphoma, and lymphoma. The study included patients who were at least 18 years old and those who were 12 to 18 years old with a body mass of at least 40 kg.²

During the dose escalation portion, patients received SLS009 monotherapy. In the dose expansion portion of the trial, the potent and highly selective CDK9 inhibitor was administered at 45 mg or 60 mg once weekly, or 30 mg twice weekly, in combination with azacitidine (Vidaza) and venetoclax.

The primary end point of the study was safety and tolerability by the incidence of dose-limiting toxicities and adverse effects. Secondary end points included ORR, duration of response, OS, progression-free survival, and pharmacokinetics.

Nearly all patients in the phase 2a trial had unfavorable/poor cytogenetic and/or molecular genetics risk (97%). Most patients were treated with continued venetoclax plus azacytidine combination therapy after experiencing relapsed or refractory disease.¹

Additional findings from the phase 2a study showed that the ORR among efficacy-evaluable patients treated at the 60 mg dose level (n = 9) was 33%; the median OS among these patients was not yet reached (NR). At the 30 mg twice weekly dose level, patients (n = 8) achieved an ORR of 50% and the median OS was NR.

Notably, 6 of 8 responders had myelodysplasia-related somatic mutations, including 5 patients with ASXL1 mutations. Patients with ASXL1 mutations achieved an ORR of 100% in the 30 mg biweekly dosing cohort.

In terms of safety, SLS009 was generally well-tolerated with no new safety signals reported across dose levels. No dose-limiting toxicities or high-grade treatment-related non-hematologic toxicities were observed. The hematologic toxicity profile did not differ from that of other venetoclax-based regimens.

In light of the positive safety and efficacy findings, the phase 2a trial has been expanded to include 2 additional cohorts at the 30 mg twice weekly dosing level. One cohort includes patients with AML harboring ASXL1 mutations and the other consists of patients with AML with myelodysplasia-related molecular mutations aside from ASXL1. Updated data from these cohorts are expected to be reported in the third quarter of 2024.

“We are excited to share very promising initial data from this phase 2a trial,” Stergiou continued in the press release.¹ “Efficacy was demonstrated across all cohorts far exceeding the targeted ORR of 20% and median OS of 3 months. The results also showed that SLS009 was well-tolerated across all doses. These data give us increased confidence in SLS009 as a potential new treatment for AML. We remain committed to advancing the treatment landscape for this underserved patient population and we look forward to continuing the trial, mainly the expansion cohorts, and reporting additional study updates and data in Q3 of this year.”

References

1. SELLAS announces completion of enrollment and initial positive data in phase 2a trial of SLS009 in r/r AML. News release. SELLAS Life Sciences Group, Inc. June 10, 2024. Accessed June 10, 2024. https://www.globenewswire.com/news-release/2024/06/10/2896012/0/en/SELLAS-Announces-Completion-of-Enrollment-and-Initial-Positive-Data-in-Phase-2a-Trial-of-SLS009-in-r-r-AML.html
2. Study of SLS009 (formerly GFH009) a potent highly selective CDK9 inhibitor in patients with hematologic malignancies. ClinicalTrials.gov. Updated June 7, 2024. Accessed June 10, 2024. https://clinicaltrials.gov/study/NCT04588922