SLS009 Demonstrates Activity, Safety in Relapsed/Refractory Lymphoma

Treatment with SLS009 (formerly GFH009) generated clinical activity and was safe in patients with relapsed/refractory lymphomas, according to topline data from the dose-escalation portion of a phase 1 trial (NCT04588922).¹

Findings showed that evaluable patients (n = 34) achieved an overall response rate (ORR) of 14.7% with a reduction in tumor burden of up to 62%. Additionally, 20.6% of patients experienced stable disease, and the disease control rate was 35.3%. Notably, in patients with peripheral T-cell lymphoma (PTCL; n = 11), the ORR was 36.4%.

Regarding safety (n = 52), SLS009 was well tolerated with no unexpected toxicities, and no drug-related deaths were reported at any dose level. The maximum tolerated dose was not reached, and 1 of 5 patients treated at the highest dose—100 mg of SLS009— experienced a dose-limiting toxicity (DLT). No DLTs occurred at lower dose levels.

The phase 1 study met all of it primary and secondary study end points, including safety, clinical activity, pharmacokinetics, and pharmacodynamics, according to an announcement from SELLAS Life Sciences Group. The recommended phase 2 dose has been established at 100 mg once per week for patients with lymphoma.

“We are excited to share strong topline data from the phase 1 trial of SLS009 in lymphoma patients, building upon the promising results in the cohort of patients with acute myeloid leukemia (AML) which we reported earlier this year,” Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS, stated in a news release. “The data demonstrate meaningful antitumor activity and clinical responses as a monotherapy. Based on its favorable therapeutic profile, SLS009 continues to emerge as a potential treatment for patients with hematologic malignancies who have exhausted available treatment options. Our partner, GenFleet Therapeutics, plans to advance SLS009 into phase 2 clinical studies in China for patients with PTCL later this year.”

The phase 1/2 trial is investigating SLS009—a small-molecule, highly selective CDK9 inhibitor—in patients with cytological or histologically confirmed relapsed/refractory hematologic malignancies, including acute myeloid leukemia, chronic lymphocytic leukemia, small lymphocytic lymphoma, and lymphoma.² Those with lymphoma need to have at least 1 measurable or evaluable lesion per 2014 Lugano response criteria and at least 2 prior lines of systemic therapy.

Key exclusion criteria consist of bulky disease of at least 10 cm requiring cytoreductive chemotherapy; symptomatic central nervous system (CNS) metastases or primary lymphoma, including primary CNS lymphoma, leptomeningeal disease, or spinal cord compression; and severe cardiovascular disease within 6 months of enrollment.

Among 52 patients with relapsed/refractory lymphoma enrolled in the phase 1 dose-escalation portion of the study, SLS009 was administered at doses ranging from 2.5 mg to 100 mg.1 Twenty-four of these patients received SLS009 twice per week, and 28 patients were given the agent once per week.

Fifteen patients had PTCL; 6 were given SLS009 twice per week, and 9 were treated once per week.

Safety is the trial’s primary end point. Secondary end points included pharmacokinetics, pharmacodynamics, and efficacy, including complete remission rate, duration of remission, progression-free survival, and overall survival.²

Among the 52 patients enrolled in the lymphoma cohort, 96% were alive at data cutoff.¹

Additional safety data showed that in patients treated with the biweekly regimen, no significant adverse effects (AEs) appeared to be dose dependent. Grade 3 or higher treatment-related AEs (TRAEs), consisting primarily of hematologic TRAEs, were reported at higher dose levels for patients treated with SLS009 once per week.

Non-hematologic, higher-grade AEs occurred in 9.6% of all patients, including hypokalemia (5.8%), upper respiratory tract infection (1.9%) and increased bilirubin (1.9%).

Pharmacodynamic data showed that a decrease in MCL1 and/or MYC biomarkers was observed in all patients treated with the once-weekly regimen in a dose-dependent manner.

References

1. SELLAS announces positive topline data in lymphoma cohort from SLS009 phase 1 dose-escalation trial, supporting advancement to phase 2 clinical study; primary and secondary endpoints met. News release. SELLAS Life Sciences Group. September 21, 2023. Accessed September 21, 2023. https://www.sellaslifesciences.com/investors/news/News-Details/2023/SELLAS-Announces-Positive-Topline-Data
2. A study of GFH009 in patients with hematologic malignancies. ClinicalTrials.gov. Updated September 1, 2023. Accessed September 21, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04588922