On September 21, 2023 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported positive topline data for the patient group with relapsed/refractory (r/r) lymphomas from the Phase 1 dose-escalation trial of its CDK9 inhibitor, SLS009 (GFH009) (Press release, Sellas Life Sciences, SEP 21, 2023, View Source [SID1234635315]).
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All primary and secondary study objectives, including safety, clinical activity, pharmacokinetics (PK), and pharmacodynamics (PD), were successfully achieved. The recommended Phase 2 Dose (RP2D) for lymphoma patients has been established at the highest dose level evaluated of 100 mg, administered as a once-weekly infusion. The maximum tolerated dose (MTD) was not reached. A dose-limiting toxicity occurred in one out of five patients treated at the 100 mg dose level. No dose-limiting toxicities were observed at any other dose level, and there were no unexpected toxicities across the study.
"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," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "The data demonstrate meaningful anti-tumor 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 GFH009 (SLS009) into Phase 2 clinical studies in China for patients with peripheral T-cell lymphoma (PTCL) later this year."
A total of 52 r/r lymphoma patients were enrolled. Of these, 24 received two bi-weekly doses (BIW), while 28 were administered weekly doses (QW). Among the 52 r/r lymphoma patients, 15 were diagnosed with PTCL, with 6 of them receiving the BIW regimen and 9 the QW regimen.
The dose-escalation trial investigated a range of doses from 2.5 mg to 100 mg, employing two dosing regiments: once-weekly infusions (QW) and twice-weekly infusions (BIW).
Key findings from the study include :
Efficacy:
Among 34 evaluable r/r lymphoma patients, five (14.7%) achieved a clinical response with a reduction in tumor burden of up to 62%.
An additional seven patients (20.6%) achieved stable disease (SD) resulting in an overall disease control rate of 35.3%.
In the subgroup of PTCL patients, four out of 11 (36.4%) evaluable patients achieved a clinical response.
Safety:
There were no drug-related fatalities at any dose level, and the drug was well tolerated.
In patients treated with the BIW regimen, no significant safety events appeared to be dose-dependent.
In patients receiving the QW regimen, ≥ G3 treatment-related adverse events (TRAEs) occurred, primarily hematologic events, at higher dose levels.
Non-hematologic toxicities were rare across all dose levels with five out of 52 patients (9.6%) experiencing higher grade toxicities, including hypokalemia (3/52 patients, 5.8%), upper respiratory tract infection (1/52 patients, 1.9%) and increase in bilirubin (1/52 patients, 1.9%).
Maximum Tolerated Dose (MTD) was not reached with only 1/5 patients at the highest dose level studied (100 mg) experiencing a dose-limiting toxicity (DLT).
No dose-limiting toxicities were observed at any other dose level, and there were no unexpected toxicities across the study.
Pharmacokinetic (PK) Data: Exposure parameters (Cmax and AUC) increased in an approximately proportional manner with the dose range of 30 mg~60 mg QW. The exposure of 100 mg was the highest, and the mean plasma concentration remained above IC90 for the longest time period (nearly 50 hours).
Pharmacodynamic (PD) Data: Desired levels of suppression in peripheral blood were achieved, leading to a decrease in MCL1 or MYC biomarkers in all (100%) studied patients. Biomarker suppression was dose-dependent in patients receiving QW dosing. The biomarkers studied included MYC and MCL1 with SLS009 administration resulted in biomarkers suppression across dose levels in both administration regimens (BIW and QW) and a dose-dependent decrease in QW groups. 100mg QW DL resulted in the longest sustained inhibition of both MCL1 and MYC.
The totality of the r/r lymphoma data will be presented at a major medical conference.
For more information on the Phase 1 study of SLS009 in r/r AML and r/r lymphomas, please visit ClinicalTrials.gov and reference Identifier NCT04588922.