Add-on therapy shows promise for hard-to-treat AML

The experimental therapy SLS009 may help improve survival for certain people with hard-to-treat acute myeloid leukemia (AML), according to new clinical trial data from the therapy’s developer, Sellas Life Sciences.

Sellas will present the analyses next month in a poster at the 68th American Society of Hematology (ASH) annual meeting in New Orleans.

“We look forward to sharing these Phase 2 results with the hematology community and the continued advancement of our SLS009 program, which is currently being studied in newly diagnosed AML patients,” Angelos Stergiou, MD, president and CEO of Sellas, said in a company press release.

AML is a form of blood cancer in which certain immune cells grow out of control. A common first-line treatment is Venclexta (venetoclax), which kills cancer cells by blocking the protein BCL2, which promotes cancer cell survival. This can be effective, but AML may relapse (come back) or be refractory (fail to respond).

“There is an urgent need in AML to address the growing number of patients who have either relapsed or become refractory to treatment with [Venclexta],” Stergiou said. “Our participation at this year’s ASH Annual Meeting reflects our continued focus on addressing this population by evaluating SLS009 in patients who have failed [Venclexta] therapy.”

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Blocking protein activity

SLS009 is designed to block the activity of CDK9, a distinct protein that can help AML cancer cells survive. By blocking CDK9, the experimental therapy aims to inhibit cancer cell survival and make AML cells more vulnerable to other cancer-killing treatments.

The new data come from a Phase 2 trial (NCT04588922) that is testing SLS009 in people with AML and other blood cancers. The study is recruiting people with newly diagnosed AML at sites across the U.S.

The data cover 62 people with AML that came back or did not respond following initial treatment with Venclexta. The patients’ median age was 70, and most had previously received two or more lines of treatment. Nearly a third (29%) had mutations affecting the TP53 protein, which normally helps regulate cell growth. Mutations in TP53 are among the main mechanisms by which AML cells can become resistant to Venclexta.

“AML patients with TP53 mutations have poor outcomes with [Venclexta]-based therapy,” said Joshua Zeidner, MD, principal investigator of the trial and a professor at the University of North Carolina Lineberger Comprehensive Cancer Center.

All patients received SLS009 in addition to Venclexta and another approved therapy, azacitidine. Efficacy data from 59 patients receiving a range of SLS009 doses showed an overall response rate of 34%; about one in three patients experienced a reduction in cancer burden after receiving the experimental treatment.

Response rates were notably higher among patients receiving SLS009 at a dose of 30 mg twice weekly, a dose selected for future testing. Among patients with TP53 mutations, more than half (57%) responded to SLS009 at this dose, and the median overall survival was 8.8 months. According to Sellas, this compares favorably against expected outcomes from patients with Venclexta-resistant and TP53-mutant AML, who would typically have a median survival time of less than three months.

Safety data from the relapsed/refractory patients suggested that the addition of SLS009 generally did not result in additional safety issues compared with what’s expected with Venclexta and azacitidine alone. Sellas said the most common side effects unrelated to blood cell counts were nausea and diarrhea, which were usually mild.

“These results show that adding SLS009 can restore responses in this setting, including in TP53-mutated disease, without adding meaningful toxicity, which matters most for patients who have struggled to remain on [Venclexta]-based treatments due to poor tolerability,” said Dragan Cicic, MD, senior vice president and chief development officer at Sellas.

Results from the part of the study in newly diagnosed AML are expected later this year. That part includes biological testing to identify patients least likely to respond to standard therapy alone.

“We have now taken SLS009 into the frontline setting, guided by precision medicine,” Cicic said. “Our extensive biological and multi-omics analyses, including genomics and single-cell profiling, help us identify which patients could benefit most and when to add SLS009 to azacitidine and [Venclexta].”

Cicic said the company expects “first topline data from the Phase 2 frontline trial in [the fourth quarter of] 2026, and we believe moving SLS009 into earlier lines of treatment will give it the best chance to change the course of this disease.”