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Tambiciclib (SLS009), a highly selective CDK9 inhibitor, generated responses and prolonged median overall survival (OS) compared with historical standards when combined with azacitidine (Vidaza) and venetoclax (Venclexta) in patients with relapsed/refractory acute myeloid leukemia (AML), meeting key end points of a phase 2 trial (NCT04588922).1
In the single-arm study, among all evaluable patients and across all cohorts and tambiciclib dose levels (n = 54), the overall response rate (ORR) was 33%; among all evaluable patients across all cohorts who received tambiciclib at the optimal dose of 30 mg twice weekly, the ORR was 40%. Patients with relapsed/refractory AML with myelodysplasia-related changes (AML MR) who received tambiciclib at the optimal dose achieved an ORR of 44%. Those with AML MR with myelomonocytic/myelomonoblastic (M4/M5) subtype (n = 12) achieved an ORR of 50%, as did those with ASXL1 mutations who received the investigational agent at the optimal dose (n = 18). All ORRs exceeded the trial’s target ORR of at least 20%.
“These [tambiciclib] results represent an important advancement for patients with relapsed/refractory AML, where treatment options remain limited and outcomes are often poor,” Yair Levy, MD, director of Hematologic Malignancies Research at Texas Oncology Baylor University Medical Center in Dallas, stated in a news release. “The response rates and survival outcomes are particularly compelling, especially given the consistency of responses across high-risk molecular subtypes and the favorable safety profile. What’s especially encouraging is the opportunity to now explore this therapy in the first-line setting, where outcomes are often dictated by how patients respond to initial treatment. The FDA’s recognition of this unmet need and its support for a trial in newly diagnosed patients reflects [tambiciclib]’s potential to address a critical gap in AML care.”
The median OS was 8.9 months in patients with AML MR and 8.8 months in those who were relapsed or refractory to venetoclax-based regimens. Furthermore, the median OS was 4.1 months among patients who had received a median of 2 prior lines of therapy. These OS durations exceeded the historical benchmark median OS with best available therapy of 2.4 months for patients who had received 1 prior line of therapy and 1.8 months for those who had received more than 1 prior line of therapy. These median OS durations also exceeded the trial’s target median OS of at least 3 months.
“We are excited to report that our phase 2 trial met all key end points, with clinical responses and survival outcomes that exceed targeted expectations and historical benchmarks,” Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS, stated in the news release. “AML remains an area of urgent unmet medical need, particularly for patients with relapsed or refractory disease, where standard treatments are often ineffective and poorly tolerated. What sets [tambiciclib] apart is its consistent efficacy across a broad range of molecular subtypes. The treatment was also well tolerated, with no dose-limiting toxicities [DLTs] across any treatment arm, validating both the biological selectivity and safety profile of our approach.”
Based on these data, the FDA has recommended the initiation of a randomized clinical trial investigating tambiciclib in the first-line setting in patients with newly diagnosed AML who are eligible for treatment with venetoclax plus azacitidine. The findings from this trial may support a new drug application seeking the approval of the agent in this population. Preparation for this trial has started, and enrollment is expected to begin by the first quarter of 2026, according to a news release from SELLAS. The trial plans to enroll 80 patients across 2 groups: those with newly diagnosed disease who are not likely to benefit from standard venetoclax plus azacitidine therapy based on molecular profiling, and those who initiate treatment with venetoclax plus azacitidine but have a confirmed lack of response after 2 treatment cycles.
“We believe earlier intervention with [tambiciclib] may offer greater clinical benefit before patients’ bone marrow reserve is depleted by disease or prior therapies, and before the disease evolves into more resistant and aggressive forms,” Dragan Cicic, MD, chief development officer of SELLAS, added in the news release. “Data from other recent clinical trials suggest meaningful differences in response rates between newly diagnosed and relapsed/refractory patients, reinforcing the importance of this strategic approach. In addition, our ongoing collaboration with one of the nation’s most prestigious cancer centers continues to generate insights in genomics, proteomics, and transcriptomics, which will refine patient selection and our precision medicine strategy and help us unlock the full potential of [tambiciclib] as we prepare to enter pivotal development.”
The open-label, multicenter phase 2 trial was designed to investigate the safety, tolerability, and efficacy of tambiciclib at 45 mg or 60 mg in combination with venetoclax and azacitidine. In the 60 mg cohort, patients received tambiciclib at either 1 60-mg dose once weekly or a 30-mg dose twice weekly. The trial was expanded to enroll patients with ASXL1-mutated AML, as well as those with myelodysplasia-related cytogenetic abnormalities beyond ASXL1 mutations.
End points of the study included the incidence of DLTs, the incidence of adverse effects, pharmacokinetics, ORR, duration of response, progression-free survival, and OS.2
The 5-cohort trial enrolled and treated 54 patients with relapsed/refractory AML who had previously progressed on venetoclax-based therapies.1 In total, 47 patients had AML MR, 23 patients had ASXL1-mutated disease; among those with AML MR, 17 had M4/M5 AML subtype. All patients had adverse-risk cytogenetics, excluding 1 patient with intermediate-risk cytogenetics. Patients had a median age of 69 years and had received a median of 2 prior lines of therapy.
Regarding safety, the addition of tambiciclib to venetoclax and azacitidine was not associated with increased toxicities compared with venetoclax plus azacitidine alone.
“We believe these data strongly support the potential of [tambiciclib] to meaningfully extend life in patients with otherwise limited options, and we look forward to sharing these findings in more detail in the future,” Stergiou concluded in the news release.
References
- SELLAS meets all primary endpoints in phase 2 trial of SLS009 in r/r AML and receives FDA guidance to advance into first-line therapy study. News release. SELLAS Life Sciences Group, Inc. July 15, 2025. Accessed July 15, 2025.
- Study of SLS009 (Formerly GFH009) a potent highly selective CDK9 inhibitor in patients with hematologic malignancies. ClinicalTrials.gov. Updated September 19, 2024. Accessed July 15, 2025. https://clinicaltrials.gov/study/NCT04588922