SELLAS Life Sciences Reports Promising Phase 2 Results for SLS009 in Venetoclax-Resistant AML at ASH 2025
核心洞察
SELLAS Life Sciences presented positive Phase 2 data showing SLS009 in combination with azacitidine and venetoclax achieved a 46% overall response rate in heavily-pretreated relapsed/refractory AML patients who had previously failed venetoclax-based therapy.
The study demonstrated particularly strong outcomes in patients with limited prior therapy, achieving a 58% response rate and median overall survival not yet reached, compared to historical benchmarks of approximately 2.5 months.
SLS009 showed encouraging activity in patients with poor prognostic mutations including ASXL1 (搜索) and TP53 (搜索), with response rates of 48% and 57% respectively, while maintaining a favorable safety profile with no dose-limiting toxicities observed.
SELLAS Life Sciences Group presented compelling Phase 2 clinical data at the 67th American Society of Hematology (ASH) Annual Meeting, demonstrating that its selective CDK9 (搜索) inhibitor SLS009 can overcome venetoclax resistance in acute myeloid leukemia patients. The combination therapy achieved meaningful response rates in a heavily-pretreated patient population with historically poor outcomes.
Strong Response Rates in Venetoclax-Resistant Population
The Phase 2 expansion study evaluated 35 patients with relapsed or refractory AML with myelodysplastic syndrome-related changes (AML-MR) who had previously failed venetoclax-based regimens. The median age was 69 years, with 98% of patients classified as having ELN adverse-risk AML. The most frequent mutations included ASXL1 (搜索), RUNX1, TP53 (搜索), and SRSF2 (搜索).
SLS009 in combination with azacitidine (AZA) and venetoclax (VEN) achieved a 46% overall response rate (CR+CRi+MLFS) across all cohorts, with 29% of patients achieving complete remission or complete remission with incomplete count recovery (CR/CRi). Notably, patients with one prior line of therapy demonstrated a 58% overall response rate.
The therapy showed particular promise in patients harboring challenging mutations. Those with ASXL1 (搜索) mutations achieved a 48% response rate (19% CR/CRi), while patients with TP53 (搜索) mutations demonstrated a 57% response rate (29% CR/CRi).
Exceptional Survival Outcomes
The survival data proved especially encouraging given the poor prognosis typically associated with this patient population. In the least pretreated cohort, median overall survival reached 8.9 months. Across all cohorts, patients with one prior line of therapy experienced median overall survival that was not yet reached, representing a dramatic improvement over the historical benchmark of approximately 2.5 months for this population.
"These results further reinforce the therapeutic potential of SLS009 to overcome resistance to venetoclax-based regimens by suppressing the expression of MCL-1, a key mechanism of resistance to BCL-2 (搜索) inhibition in AML," said Dr. Dragan Cicic, Senior Vice President and Chief Development Officer of SELLAS.
Favorable Safety Profile
The combination demonstrated a favorable safety profile, with SLS009 administered at 30 mg intravenously twice weekly added to standard AZA/VEN therapy. No dose-limiting toxicities (DLTs) or treatment-related deaths were observed throughout the study, and the combination was well tolerated by patients.
Expansion into Newly Diagnosed AML
Building on these positive results, SELLAS plans to expand the study to evaluate SLS009 plus AZA/VEN in newly diagnosed AML patients with high-risk features. The company expects enrollment for this expansion to begin in the first quarter of 2026, representing an 80-patient trial that will include both newly diagnosed AML patients and those who become refractory early to AZA/VEN treatment.
Broader Development Program
Beyond AML, SELLAS has demonstrated SLS009's potential across multiple hematologic malignancies. In October 2025, the company presented preclinical data at the European Society for Medical Oncology (ESMO) Congress showing statistically significant survival benefits of SLS009 in T-cell prolymphocytic leukemia (T-PLL) models, both as monotherapy and in combination with venetoclax.
The company describes SLS009 (tambiciclib) as potentially the first and best-in-class differentiated small molecule CDK9 (搜索) inhibitor with reduced toxicity and increased potency compared to other CDK9 inhibitors. The drug has demonstrated high response rates in AML patients with unfavorable prognostic factors, including ASXL1 (搜索) mutations commonly associated with poor prognosis in various myeloid diseases.
SELLAS recently strengthened its financial position, receiving approximately $54.6 million in gross proceeds from warrant exercises in September and October 2025, providing resources to advance its clinical development programs.