FDA Grants Fast Track Status to SLS009 for Relapsed/Refractory Acute Myeloid Leukemia

The FDA has granted fast track designation to SLS009 (formerly GFH009) for use as a potential therapeutic option in patients with relapsed or refractory acute myeloid leukemia (AML), according to an announcement from SELLAS Life Sciences Group, Inc.¹

The safety and efficacy of the CDK9 inhibitor in combination with venetoclax (Venclexta) and azacitidine (Vidaza) in this population is being explored as part of an ongoing phase1/2 study (NCT04588922).²

Of the 9 patients enrolled to the safety cohort who were given SLS009 at 45 mg in combination with the doublet, 8 remain alive and 6 are still on treatment. At a follow-up ranging from 2 to 7 months for those still alive, the median overall survival (OS) had not yet been reached. Seven out of 8 evaluable patients were found to experience significant antileukemia effects defined as having a decrease of at least 50% in bone marrow blasts. To date, no dose-limiting toxicities and no significant safety signals have been observed.

Findings from the phase 1 portion showed that when SLS009 was given as a single agent, it elicited a complete response (CR) that proved to be durable in a patient who had AML and experienced failure with previous venetoclax/azacitidine. Moreover, no minimal residual disease was observed in this patient who continues to be alive at 16 months post-treatment initiation.

“Receiving fast track designation for SLS009 for relapsed or refractory AML, following the recent orphan drug designation for the same indication, underscores the potential for SLS009 and highlights the critical unmet need for patients with AML who face a poor prognosis due to the progressive nature of the disease,” Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS Life Sciences Group, Inc., stated in a press release. “The initial positive topline phase 2a data at the 45-mg [safety] dose level demonstrate that SLS009 in combination with venetoclax and azacitidine exhibits antileukemic effects with a favorable safety profile in AML patients resistant to venetoclax combination therapies.”

The open-label, single-arm, multicenter study enrolled patients with cytologically or histologically confirmed relapsed or refractory hematologic malignancies, including AML, chronic lymphocytic leukemia or small lymphocytic lymphoma, and lymphoma.² They needed to be at least 18 years of age, have at least 1 measurable or evaluable lesion by 2014 Lugano response criteria, and have previously received at least 2 lines of systemic treatment. Those in the phase 2a AML combination cohort needed to be relapsed or refractory to previous venetoclax-containing regimens.

If patients had bulky disease that was at least 10 cm and required receipt of cytoreductive chemotherapy, symptomatic central nervous system metastases or primary lymphoma, or severe cardiovascular disease within 6 months of enrollment, they were excluded.

In the phase 2a portion of the research, SLS009 is under evaluation at 2 doses: 45 mg and 60 mg; both doe cohorts will also receive venetoclax and azacitidine.¹ Those included in the 60-mg cohort were randomly assigned into 1 of 2 groups: those who were given a fixed dose of 60 mg once weekly or those given a fixed dose of 30 mg twice weekly. Each group is slated to enroll 5 to 10 participants.

Primary end points of the study include safety, tolerability, composite CR rate, and duration of response. Investigators will also assess event-free survival, OS, pharmacokinetics, and pharmacodynamics.

Previous data shared in October 2023 indicated that of 5 patients enrolled and treated in the safety 45-mg dose cohort, 1 achieved a CR and had been in the fifth month of treatment following relapse on venetoclax.³ Another patient was still alive and in the fourth month of treatment with the regimen. At that time point, all enrolled patients were still alive and 4 total were still on treatment. All patients were noted to have experienced antileukemic effects without substantial safety concerns.

“We have now also enrolled several patients in the ongoing 60-mg dose cohort,” Stergiou added in the press release.¹ “Our team is committed to advancing the development of SLS009 with the goal of providing effective solutions to patients in need of viable treatment options.”

Additional data from the safety 45-mg cohort is anticipated in the first quarter of 2024, as are initial findings from the 60-mg cohort, which is the recommended phase 2 dose of SLS009. The 60-mg cohort will be assessed in the second quarter of this year.

References

1. 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, 2024. Accessed January 10, 2024. https://www.sellaslifesciences.com/investors/news/News-Details/2024/SELLAS-Life-Sciences-Receives-FDA-Fast-Track-Designation-for-SLS009-for-Treatment-of-RelapsedRefractory-Acute-Myeloid-Leukemia-and-Provides-Updated-Data-for-Phase-2a-Study-of-SLS009-in-RelapsedRefractory-Acute-Myeloid-Leukemia-Patients/default.aspx
2. A study of GFH009 in patients with hematologic malignancies. ClinicalTrials.gov. Updated September 1, 2023. Accessed January 10, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04588922
3. SELLAS announces positive initial topline phase 2a data of SLS009 in acute myeloid leukemia. News release. SELLAS. October 16, 2023. Accessed January 10, 2024. https://www.sellaslifesciences.com/investors/news/News-Details/2023/SELLAS-Announces-Positive-Initial-Topline-Phase-2a-Data-of-SLS009-in-Acute-Myeloid-Leukemia/default.aspx