SLS009 Plus Venetoclax/Azacitidine Produces Responses in R/R AML, Including ASXL1+ Disease

Treatment with the small molecule, highly selective CDK9 inhibitor SLS009 (formerly GFH009) in combination with venetoclax (Venclexta) and azacitidine (Vidaza) generated responses in patients with relapsed/refractory acute myeloid leukemia (AML), including those harboring ASXL1 truncating mutations, according to phase 2a data from a phase 1/2 trial (NCT04588922).¹

Findings showed that among all patients treated with the optimal dose of SLS009 at 30 mg twice per week, SLS009 elicited an overall response rate (ORR) of 57%, passing the targeted ORR of 20%. Notably, patients harboring ASXL1 mutations who were treated at the optimal dose (n = 4) achieved an ORR of 100%, which comprised complete responses (CRs), CRs with incomplete hematologic recovery (CRi), and morphologic leukemia–free state (MLFS). All 4 patients were still alive at data cutoff. In patients with ASXL1-mutated disease treated across all dose levels of SLS009 (n = 8), the ORR was 63%.

“The remarkable responses achieved in patients with the ASXL1 mutation underscores the transformative potential of SLS009 in addressing the unmet medical needs of AML but also targeting colorectal cancer and other tumor types with this alteration,” Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS Life Sciences Group, stated in a news release. “This is evidenced by strong enthusiasm from the participating investigators reflected in robust enrollment from the clinical sites. These compelling results from the phase 2a study further reinforce our belief that SLS009 represents a potential breakthrough for relapsed and/or refractory AML patients, and could pave the way for a potential accelerated approval in this defined patient population.”

Based on the phase 2a data, SELLAS intends to begin discussions with the FDA regarding potential accelerated approval for SLS009 for the treatment of patients with relapsed/refractory AML harboring ASXL1 mutations, as well as for patients harboring this mutation in other indications. In AML, ASXL1 mutations occur in approximately 20% of patients, and they are an unfavorable prognostic factor regarding survival and are also associated with lower CR rates.

The open-label, single-arm, multicenter phase 1/2 study enrolled patients with cytologically or histologically confirmed relapsed or refractory hematologic malignancies, including AML, chronic lymphocytic leukemia/small lymphocytic lymphoma, and lymphoma. In the phase 2a portion, patients with AML were required to have disease that relapsed on or was refractory to venetoclax-containing regimens.^1,2

Key exclusion criteria included bulky disease requiring cytoreductive therapy; symptomatic central nervous system (CNS) metastases or primary lymphoma, such as primary CNS lymphoma, leptomeningeal disease, or spinal cord compression; and severe cardiovascular disease within 6 months of study entry.²

In the phase 2a study, patients received venetoclax/azacitidine in combination with SLS009 at 1 of 2 dose levels: 45 mg and 60 mg. In the 60-mg cohort, patients were randomly assigned to receive SLS009 at 60 mg once per week or 30 mg twice per week.¹

The primary end points of the study were safety and tolerability. Secondary end points included pharmacokinetics, CR rate, duration of response, progression-free survival, and overall survival (OS).²

In phase 2a, the target ORR was 20% for the optimal dose of SLS009, and the target median OS was 3 months.1 Going forward, an expansion cohort will enroll patients with relapsed/refractory AML harboring ASXL1 mutations.

Previously reported data from the phase 2a portion of the trial showed that patients with relapsed/refractory AML treated with SLS009 at the optimal dose in combination with venetoclax and azacitidine experienced an ORR of 50%.³

References

1. SELLAS announces positive phase 2 preliminary data of SLS009 in r/R AML achieving a 100% response rate in patients with ASXL1 mutation at the optimal dose level. News release. SELLAS Life Sciences Group. May 1, 2024. Accessed May 1, 2024. https://ir.sellaslifesciences.com/news/News-Details/2024/SELLAS-Announces-Positive-Phase-2-Preliminary-Data-of-SLS009-in-rr-AML-Achieving-a-100-Response-Rate-in-Patients-with-ASXL1-Mutation-At-the-Optimal-Dose-Level/default.aspx
2. A study of GFH009 in patients with hematologic malignancies. ClinicalTrials.gov. Updated September 9, 2023. Accessed May 1, 2024. https://clinicaltrials.gov/study/NCT04588922
3. SELLAS announces positive topline data from the phase 2a study of SLS009 in r/r AML and provides steering committee update on phase 3 REGAL study. News release. SELLAS Life Sciences Group. March 26, 2024. Accessed May 1, 2024. https://ir.sellaslifesciences.com/news/News-Details/2024/SELLAS-Announces-Positive-Topline-Data-from-the-Phase-2a-Study-of-SLS009-in-rr-AML-and-Provides-Steering-Committee-Update-on-Phase-3-REGAL-Study/default.aspx