Novel CDK9 Inhibitor Yields Responses in Relapsed/Refractory AML

In January 2024, the FDA granted fast track designation to SLS009.

Positive topline results from a phase 2a trial (NCT04588922) assessing SLS009 plus azacitidine and venetoclax (Venclexta) in a small cohort of patients with acute myeloid leukemia (AML) were announced by SELLAS Life Sciences Group, Inc.¹

As of the March 15, 2024 cutoff date, 21 patients had been treated. After prior venetoclax-containing regimens were given, all patients were diagnosed with relapsed/refractory AML. Of those enrolled, 95% had high-risk cytogenetics, and 90.5% were older than 60.

Multiple dosing cohorts were assessed in this trial. Overall, 10 patients were assigned to the 45 mg group, and 11 were assigned to the 60 mg group given either twice a week at 30 mg or once a week at 60 mg. In the 30 mg twice-a-week group, a 50% response rate was observed, and a 20% response rate was observed in the 60 mg once a week. For those receiving 45 mg, there was a 10% response rate.

Of note, strong anti-leukemic activity was observed with 50% or more bone marrow blast reduction in 67% of patients across all dose levels. At the time of cutoff, the median survival rate had not been reached. The first patient in the trial to have been enrolled and achieve a response is still on study treatment and is leukemia-free after 9 months.

Regarding safety, the combination had been well-tolerated at all dose levels, and no dose-limiting toxicities were observed. For the azacitidine/venetoclax regimen, hematologic malignancies were consistent with previous findings.

“We are extremely excited to share positive topline data from the phase 2a trial of SLS009 in [patients with] AML [who are] resistant to venetoclax combination therapies… These compelling results from phase 2a reinforce our belief that SLS009 represents a potential breakthrough for patients with relapsed and/or refractory AML, addressing one of the most urgent unmet medical needs,” Angelos Stergiou, MD, ScD, president and chief executive officer at SELLAS, said in the press release.

The press release also provided an update on the phase 3 REGAL trial (NCT04229979), which will assess galinpepimut-S (GPS) vs best available treatment in patients with AML in second complete remission or in second complete remission with incomplete platelet recovery.

On March 22, 2024, the REGAL steering committee met to discuss the high number of patients enrolled; the interim analysis, which requires 60 events, may occur soon. An independent data monitoring committee is set to meet at the end of April.

“As of this evaluation, 123 patients were enrolled with 66 of them discontinuing the treatment. In the trial, patients are recorded as having stopped the study treatment in cases of death for any reason, relapse, intolerable toxicity, or treatment completion. Regarding the GPS arm, we are pleased to report that we have not observed any intolerable toxicities in any patient population across all our clinical studies thus far, although toxicities are commonly observed with therapies used in the control arm. Therefore, almost all patients who are off treatment may have most likely either relapsed or passed away,” Stergiou continued.

In January 2024, the FDA granted fast track designation to SLS009.² At the time, only 9 patients had been enrolled at the 45 mg dose level, with 8 patients alive and 6 still receiving treatment.

Orphan drug designation was granted to SLS009 in October 2023 for the phase 1 portion of the trial. At this time, there was a 77.3% reduction in bone marrow blast following treatment with SLS009.³

References

1. SELLAS announces positive topline data from the phase 2a study of SLS00- in r/r AML and provides steering committee update on phase 3 REGAL study. News release. SELLAS Life Sciences Group, Inc. March 26, 2024. Accessed March 28, 2024. https://shorturl.at/stI36
2. SELLAS Life Sciences receives FDA fast track designation for SLS009 for treatment of relapsed/refractory acute myeloid leukemia and provides updated data for phase 2a study of SLS009 in relapsed/refractory acute myeloid leukemia patients. News release. SELLAS Life Sciences Group, Inc. January 9, 2023. Accessed March 28, 2024. https://bit.ly/48jO0QV
3. SELLAS receives FDA orphan drug designation for SLS009 for treatment of acute myeloid leukemia. News release. SELLAS Life Sciences Group, Inc. October 10, 2023. Accessed March 28, 2024. https://tinyurl.com/3n3e3s3p