Sellas Life Sciences' CDK9 Inhibitor Shows Promise in Phase 2 AML Study

Sellas Life Sciences has reported encouraging results from a phase 2 study of its investigational CDK9 inhibitor, SLS009 (tambiciclib), in patients with acute myeloid leukemia (AML). The open-label, single-arm trial demonstrated an overall response rate (ORR) that more than doubled the company's initial target, potentially offering new hope for patients with limited treatment options.

Study Design and Patient Population

The phase 1/2a study evaluated SLS009 in combination with venetoclax (Venclexta/Venclyxto) and azacitidine (Vidaza) in 54 evaluable patients with advanced AML who had not previously responded to venetoclax-based therapies. The trial focused on two key patient subgroups:

• 87% of patients had AML with myelodysplasia-related changes (AML MR)
• 43% of patients harbored ASXL1 mutations, often associated with poor prognosis

SLS009 was administered at two dose levels: 45 mg and 60 mg. In the higher dose cohort, patients received either 60 mg once weekly or 30 mg twice weekly.

Efficacy Results Exceed Expectations

The primary endpoint of ORR was met across multiple patient subgroups, surpassing both the company's target and historical benchmarks:

• 44% ORR in AML MR patients receiving 30 mg twice weekly
• 50% ORR in patients with AML MR myelomonocytic/myelomonoblastic (M4/M5) subtype
• 50% ORR in patients with ASXL1 mutations receiving 30 mg twice weekly
• 33% ORR across all evaluable patients

Notably, the median overall survival (mOS) also exceeded expectations:

• 8.9 months mOS for patients with AML MR
• 8.8 months mOS for patients with one prior line of therapy receiving 30 mg twice weekly, compared to a historical benchmark of 2.4 months
• 4.1 months mOS for patients with two prior lines of therapy, versus a 1.8-month benchmark

Safety Profile and Future Development

The safety profile of SLS009 in combination with venetoclax and azacitidine was consistent with that observed for venetoclax and chemotherapy alone, with no dose-limiting toxicities reported.

Based on these promising results and FDA recommendations, Sellas is planning to initiate a randomized trial in newly diagnosed AML patients. The company aims to launch this 80-patient study by Q1 2026, with the potential to support a new drug application.

Dr. Yair Levy, Director of Hematologic Malignancies Research at Texas Oncology Baylor University Medical Center, commented on the significance of the results: "These SLS009 results represent an important advancement for patients with relapsed/refractory AML, where treatment options remain limited and outcomes are often poor. 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."