Tambiciclib Plus Ven/Aza Met All Primary End Points in R/R AML Trial

Tambiciclib with venetoclax and azacitidine exceeded the target ORR of 20%, achieving an ORR of 44% in patients with AML-myelodysplasia-related changes who were treated at the 30 mg twice-weekly dose.

The highly selective CDK9 inhibitor tambiciclib (SLS009) met all primary end points for the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) in a phase 2 trial (NCT04588922), according to a news release from the developer, SELLAS Life Sciences Group.1

Tambiciclib with venetoclax (Venclexta) and azacitidine (Vidaza) exceeded the target overall response rate (ORR) of 20%, achieving an ORR of 44% in patients with AML-myelodysplasia-related changes (AML MR) who were treated at the 30 mg twice-weekly dose, and an ORR of 50% in AML MR with myelomonocytic or myelomonoblastic subtype.

In all evaluable patients, the ORR was 33% across all cohorts and dose levels, and 40% at the 30 mg twice-weekly dose level. Patients with ASXL1 mutations demonstrated an ORR of 50% at the 30 mg twice a week dosage.

The median overall survival (OS) was 8.9 months in patients with AML MR, and 8.8 months in those who were relapsed/refractory to venetoclax-based regimens who received 30 mg twice-weekly; the investigators noted that this exceeded the historical benchmark of 2.4 months.

The median OS in cohorts with a median of 2 prior lines of therapy was 4.1 months vs 1.8 months with best available therapy.

“We are excited to report that our phase 2 trial met all key endpoints, 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 press release.1 “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 trial had a total of 54 evaluable patients with relapsed/refractory AML who previously progressed on venetoclax-based therapies. All enrolled patients were split into 5 cohorts: cohort 1, patients received 45 mg once a week; cohort 2, patients received 60 mg once-weekly; cohort 3, patients received 30 mg twice a week; cohort 4, patients with ASXL1 mutations received 30 mg twice-weekly; and cohort 5, patients with other than ASXL1 mutations received 30 mg twice a week.2

Eligible patients were 18 years or older, or 12 to 18 years with a weight of 40 kg or more, and cytologically or histologically confirmed relapsed/refractory hematologic malignancies.

The median age of patients was 69 years, with a median number of prior lines of therapy of 2. All but 1 patient had adverse risk cytogenetics, who instead had intermediate risk cytogenetics.

The primary end point of the trial was ORR. Secondary end points included OS, duration of response, progression-free survival, OS, and safety and tolerability.

The trial combination of tambiciclib plus venetoclax and azacitidine was well tolerated; the addition of tambiciclib did not result in increased toxicities compared to venetoclax and azacitidine alone. No dose-limiting toxicities were observed across all dose levels.

The FDA has recommended that the developer proceed into a trial to include patients with newly diagnosed first-line AML who are eligible for venetoclax and azacitidine therapy. This trial is expected to begin enrollment in the first quarter of 2026. There will be a predictive biomarker cohort of newly diagnosed patients who are unlikely to benefit from the therapy based on molecular profiling, and there will be an early resistance cohort of patients who initiate treatment with venetoclax and azacitidine but demonstrate a lack of confirmed response after 2 treatment cycles.

“These [tambiciclib] results represent an important advancement for patients with R/R AML, where treatment options remain limited and outcomes are often poor,” said Yair Levy, MD, director of Hematologic Malignancies Research at Texas Oncology Baylor University Medical Center, in the news release.1 “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.”

References

1. 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. July 15, 2025. Accessed July 16, 2025. https://tinyurl.com/mrjpzw36
2. Study of SLS009 (Formerly GFH009) a potent highly selective CDK9 inhibitor in patients with hematologic malignancies. ClinicalTrials.gov. Updated September 19, 2024. Accessed July 16, 2026. https://tinyurl.com/wbe5ujts