FDA Grants Fast Track Designation to SLS009 for Relapsed/Refractory PTCL

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The FDA has granted a fast track designation to SLS009 for the treatment of patients with relapsed/refractory peripheral T-cell lymphoma.

The FDA has granted a fast track designation to SLS009 (formerly GFH009) for the treatment of patients with relapsed/refractory peripheral T-cell lymphoma (PTCL), according to an announcement from SELLAS Life Sciences Group.¹

The fast track designation follows the readout of topline data from a phase 1 trial (NCT04588922), which showed that SLS009 elicited clinical activity and was well tolerated in patients with relapsed/refractory lymphomas.² Evaluable patients (n = 34) experienced an overall response rate (ORR) of 14.7% with a reduction in tumor burden of up to 62%. Furthermore, stable disease was reported in 20.6% of patients, and the disease control rate was 35.3%.

In patients with relapsed/refractory PTCL (n = 11), the ORR was 36.4%.

No unexpected toxicities or drug-related deaths occurred at any dose level of SLS009. A dose-limiting toxicity (DLT) was observed in 1 of 5 patients treated at the highest dose level of 100 mg of SLS009; however, no DLTs were reported at lower dose levels.

SELLAS, the developer of the drug, previously announced that the phase 1 trial met all its primary and secondary end points. The recommended phase 2 dose will be 100 mg once per week for patients with lymphoma.

“The FDA’s decision to grant SLS009 fast track designation signifies an important milestone towards developing a safe and effective treatment for [patients with] PTCL, a group of aggressive and rare non-Hodgkin lymphomas, and underscores the urgent need for innovative therapies such as SLS009 that can significantly improve the outcome of [patients with] PTCL,” Angelos Stergiou, MD, ScD hc, president and chief executive officer of SELLAS, stated in a news release.¹

SLS009 is a small-molecule, highly selective CDK9 inhibitor being evaluated in the phase 1/2 trial in patients with cytologically or histologically confirmed relapsed/refractory hematologic malignancies, including acute myeloid leukemia (AML), chronic lymphocytic leukemia, small lymphocytic lymphoma, and lymphoma.^1,3 Patients with lymphoma are required to have at least 1 measurable or evaluable lesion per 2014 Lugano response criteria and at least 2 prior lines of systemic therapy.

Patients are being excluded if they have 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.

Patients with relapsed/refractory lymphoma treated in the dose-escalation portion of the study thus far (n = 52) received SLS009 at doses ranging from 2.5 mg to 100 mg either twice per week (n = 24) or once per week (n = 28).²

Among enrolled patients, 15 patients had PTCL, and they were treated twice per week (n = 6) or once per week (n = 9).

Safety is serving as the trial’s primary end point. Secondary end points include pharmacokinetics, pharmacodynamics, and efficacy, such as complete remission rate, duration of remission, progression-free survival, and overall survival.³

Ninety-six percent of enrolled patients were alive at data cutoff.²

Further safety data showed that no significant adverse effects (AEs) appeared to be dose dependent. Grade 3 or higher treatment-related AEs (TRAEs), which were primarily hematologic TRAEs, occurred at higher dose levels for patients treated with SLS009 once per week.

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

“SLS009 has demonstrated very promising clinical responses in [patients with] PTCL in the recently completed dose-escalation portion of the Phase 1 trial in relapsed/refractory hematological malignancies, and with the Fast Track designation, we are poised to accelerate its development,” Stergiou added.1 “We are committed to working closely with the FDA and our partner GenFleet Therapeutics to develop this promising treatment for patients in need.”

On October 11, 2023, the FDA also granted an orphan drug designation to SLS009 for the treatment of patients with AML.⁴