Tambiciclib Combo Shows Activity in Relapsed/Refractory Post-Venetoclax AML

The addition of tambiciclib (SLS009), a highly selective CDK9 inhibitor, to azacitidine (Vidaza) and venetoclax (Venclexta) produced encouraging response and survival outcomes with no meaningful added toxicity in patients with relapsed or refractory acute myeloid leukemia (AML) who had previously progressed on venetoclax-based therapy, according to a press release on results from a phase 2 study (NCT04588922) from the developer, SELLAS Life Sciences.¹ The developers noted that detailed findings will be presented at the 2026 American Society of Hematology (ASH) Annual Meeting and Exposition.

What were the efficacy outcomes?

Across all doses evaluated in the dose-ranging study (n = 59), the overall response rate (ORR) was 34%, comprising 12 patients with a complete remission or complete remission with incomplete hematologic recovery (CR/CRi) and 8 with a morphologic leukemia-free state. Response rates were 38% in patients with AML with myelodysplasia-related changes, 44% in monocytic AML, and 36% in TP53-mutated AML.

At the selected dose of 30 mg twice weekly, patients with monocytic AML achieved a 54% ORR and a median overall survival (OS) of 5.8 months, while patients with TP53-mutated AML achieved a 57% ORR and a median OS of 8.8 months. These outcomes, the developer stated, compare favorably with a historical median OS of approximately 2.5 months in these adverse-risk settings.

What was the safety profile?

The addition of tambiciclib to azacitidine and venetoclax was well tolerated, with limited additive toxicities and treatment-related deaths reported. Non-hematologic treatment-related adverse events (AEs) were predominantly mild grade 1 or 2 nausea and diarrhea.

“[Patients with AML] who progress after venetoclax-based therapy have very limited treatment options. Venetoclax resistance is largely driven by MCL-1 dependence. Furthermore, [patients with AML] with TP53 mutations have poor outcomes with venetoclax-based therapy,” said principal investigator Joshua F. Zeidner, MD, a professor of medicine and chief of leukemia research at the University of North Carolina Lineberger Comprehensive Cancer Center, in the news release.¹ “The response rates of 57% in relapsed TP53-mutated and 54% in relapsed monocytic AML are encouraging and suggest that SLS009 acts on the biology that drives resistance. Continued investigation of SLS009 in combination with azacitidine and venetoclax in the frontline setting is now a natural development course for this therapy.”

What was the study design and population?

The completed phase 2 dose-ranging study evaluated tambiciclib, a highly selective CDK9 inhibitor, in combination with azacitidine and venetoclax in patients with relapsed/refractory AML following prior venetoclax-based treatment. The trial enrolled 62 patients with heavily pretreated disease; the median age was 70 years, and the median number of prior lines of therapy was 2, with a maximum of 8. High-risk mutations were common, including ASXL1 (41%), RUNX1 (33%), and TP53 (29%).

The trial’s primary end points included dose-limiting toxicities, AEs, and ORR.² Secondary end points included duration of response, progression-free survival, OS, and pharmacokinetics.

What are the next steps?

The developers have advanced tambiciclib into the frontline setting, with enrollment and dosing ongoing in an 80-patient phase 2 trial in patients with newly diagnosed AML—including those identified as becoming refractory early to azacitidine and venetoclax through transcriptomic, genomic, and proteomic profiling—with early topline data expected in the fourth quarter of 2026. The phase 2 relapsed/refractory results will be presented in a poster session (Abstract 5155) on December 14, 2026, at the ASH Annual Meeting in New Orleans.

References

1. SELLAS Life Sciences to present positive phase 2 data demonstrating encouraging response and survival outcomes with SLS009 combination in high-risk AML at ASH 2026. News release. SELLAS Life Sciences Group, Inc. November 4, 2026. Accessed November 6, 2026. https://tinyurl.com/4sf4kru9
2. Study of SLS009 (formerly GFH009) a potent highly selective CDK9 inhibitor in patients with hematologic malignancies and high-risk newly diagnosed AML. ClinicalTrials.gov. Updated September 3, 2026. Accessed November 6, 2026. https://tinyurl.com/3r5bc27w