Tambiciclib Generates Potential OS Benefit in R/R AML

Acute Myeloid Leukemia |

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The highly selective CDK9 inhibitor tambiciclib (SLS009; formerly GFH009) yielded a potential overall survival (OS) benefit among patients with relapsed/refractory acute myeloid leukemia (AML), according to data from cohort 3 of a phase 2 trial (NCT04588922) announced by SELLAS Life Sciences Group.1

Finding showed that efficacy-evaluable patients treated in cohort 3 (n = 13) achieved a median OS of 8.8 months; those with AML with myelodysplasia-related cytogenetics (MRC; n = 10) achieved a median OS of 8.9 months.

Additionally, the overall response rate (ORR) was 46% for all patients enrolled in cohort 3 and 67% for patients with AML MRC. In patients with myelomonocytic AML (n = 4), the ORR was 75%. Regarding safety, tambiciclib was well tolerated and no new safety signals were reported.

“The remarkable results from cohort 3 of the ongoing phase 2 trial reinforce the potential of [tambiciclib] to transform outcomes for these heavily pretreated [patients with] AML,” Angelos Stergiou, MD, ScDhc, president and CEO of SELLAS, stated in a news release. “Not only have we observed unprecedented survival benefits, but the high [ORR] underscores the therapy’s efficacy profile. The data reveal that [patients who were] relapsed or refractory to venetoclax [Venclexta]-based regimens receiving 30 mg twice per week achieved a median OS of 8.8 months, far surpassing the historical benchmark of 2.5 months.”

The ongoing open-label, multicenter, nonrandomized phase 2 study is enrolling patients with cytologically or histologically confirmed relapsed/refractory hematologic malignancies who are at least 18 years or 12 to 18 years of age with a body mass of at least 40 kg.2 In cohort 3, patients with AML are required to have disease that is relapsed/refractory to venetoclax-based regimens. Cohort 4 comprises patients with relapsed/refractory AML harboring an ASXL1 mutation following a venetoclax-containing regimen, and cohort 5 is enrolling patients with relapsed/refractory AML following treatment with a venetoclax-containing regimen who harbor mutations other than ASXL1.

The study excludes patients with bulky disease—defined as at least 10 cm—who require cytoreductive therapy; those with symptomatic central nervous system (CNS) metastases or primary lymphoma, including primary CNS lymphoma, leptomeningeal disease, or spinal cord compression; and patients with severe cardiovascular disease within 6 months of enrollment.

The first 2 groups enrolled during the study served as dose-escalation arms that evaluated tambiciclib in patients with relapsed/refractory AML (cohort 1) and relapsed/refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, or lymphoma (cohort 2). In group 3, patients with relapsed/refractory AML received tambiciclib at 45 mg once per week (cohort 1), 60 mg once per week (cohort 2), or 30 mg twice per week (cohort 3). Patients in cohorts 4 and 5 also received tambiciclib at 30 mg twice per week.

Safety and the incidence of dose-limiting toxicities are the trial’s primary end points. Secondary end points include pharmacokinetics, ORR, duration of response, progression-free survival, and OS.

Among all patients enrolled in cohort 3 (n = 14), the median age was 71 years (range, 35-89), and patients received a median of 1 prior line of therapy (range, 1-6).1 Among the 10 patients with AML MRC, 4 patients had a myelomonocytic phenotype. Mutations observed in this cohort included ASXL1 (n = 6), RUNX1 (n = 5), and TP53 (n = 3). Notably, all patients had adverse-risk cytogenetics per ELN 2022 criteria.

Additional data showed that the ORR was 67% in patients harboring ASXL1 mutations, 60% in those with RUNX1 mutations, and 33% in patients with TP53 mutations.

“The therapy demonstrated a 67% ORR in patients with AML-MRC and 46% in all evaluable patients, significantly exceeding the targeted 20% ORR,” Stergiou added in the news release. “With responses seen across different genetic mutations, this approach could be transformational for many underserved patients. We are continuing to explore [tambiciclib’s] potential in expansion cohorts to further validate its potential to address critical unmet medical needs.”

References

1. SELLAS announces positive overall survival in cohort 3 from the ongoing phase 2 trial of SLS009 in R/R AML. News release. Sellas Life Sciences Group. April 8, 2025. Accessed April 8, 2025. https://ir.sellaslifesciences.com/news/News-Details/2025/SELLAS-Announces-Positive-Overall-Survival-in-Cohort-3-from-the-Ongoing-Phase-2-Trial-of-SLS009-in-rr-AML/default.aspx
2. Study of SLS009 (formerly GFH009) a potent highly selective CDK9 inhibitor in patients with hematologic malignancies. ClinicalTrial.gov. Updated September 19, 2024. Accessed April 8, 2025. https://clinicaltrials.gov/study/NCT04588922