SLS009 Phase 2 Results: 100% Response in r/r AML with ASXL1 Mutation

On May 1, 2024, SELLAS Life Sciences Group, Inc. (NASDAQ: SLS), a clinical biopharmaceutical company focused on cancer therapies, announced preliminary results from its Phase 2a trial of SLS009, a highly selective CDK9 inhibitor, used to treat relapsed/refractory acute myeloid leukemia (r/r AML). The study also incorporated a provisional patent application concerning the ASXL1 mutation and SLS009, which encompasses all CDK9 inhibitor drugs. ASXL1 mutations are known to predict poor prognosis in myeloid diseases due to subpar responses to current treatments.

SELLAS has reported promising responses in patients with myelodysplasia-related molecular mutations, particularly the ASXL1 mutation, which was the most common among responders across all dose groups. Consequently, the Phase 2 trial for r/r AML has been expanded to include two new cohorts: one consisting of AML patients with ASXL1 mutations and another group of patients with myelodysplasia-related molecular abnormalities other than ASXL1.

“These early results are promising and could signify a novel approach in treating AML and possibly other conditions,” remarked Dr. Joshua Zeidner, the study’s principal investigator and an Associate Professor at the University of North Carolina Lineberger Comprehensive Cancer Center. Dr. Zeidner emphasized that ASXL1 is a relatively common mutation in AML, associated with poor outcomes with existing treatments. No targeted therapies are currently effective for these patients, and he expressed optimism that SLS009 could significantly impact the management of AML patients with ASXL1 mutations and potentially other related myeloid diseases.

Key points from the study include:

1.As of the data cutoff on April 19, 2024, an overall response rate of 57% has been achieved with the optimal dose regimen of 30 mg BIW, surpassing the targeted 20% rate.
2.All four (100%) r/r AML patients with ASXL1 truncating mutations at the selected dose level achieved an overall response and are alive.
3,63% (5 out of 8) of r/r AML patients across all dose levels with ASXL1 truncating mutations responded to SLS009.
4.A patient in the Phase 1 trial who achieved a complete remission lasting over 8 months also had an ASXL1 mutation.
5.The ASXL1 mutation is present in both hematological malignancies and solid tumors.
6.All study participants have AML that is refractory to or has relapsed after treatments containing venetoclax. Future enrollment and treatment will prioritize participants in the expansion cohort diagnosed with the ASXL1 mutation, receiving the 30 mg BIW dose.
Angelos Stergiou, the President and CEO of SELLAS, highlighted the significance of the results, stating that the responses observed among patients with the ASXL1 mutation demonstrate SLS009's transformative potential in meeting unmet medical needs not only in AML but potentially in colorectal and other tumor types with this genetic alteration. He mentioned the strong enthusiasm among participating investigators and robust enrollment at clinical sites, suggesting that these compelling Phase 2a results reinforce the possibility of SLS009 as a groundbreaking treatment for relapsed and/or refractory AML patients and might justify accelerated approval.

SELLAS aims to engage with the U.S. Food and Drug Administration (FDA) to discuss the potential for an accelerated approval path for SLS009 in the ASXL1 mutation-defined r/r AML patient population and other related indications.

The Phase 2a trial of SLS009 is an open-label, single-arm, multi-center study to evaluate the safety, tolerability, and efficacy of SLS009 alongside aza/ven at two dose levels, 45 mg and 60 mg. Patients in the 60 mg dose group were randomized to either a 60 mg dose once per week or 30 mg twice weekly. The trial targets a 20% response rate at the optimal dose level, with a median survival over 3 months. Additionally, the study aims to identify biomarkers for target patient populations to inform future trials.