Among the 25 patients with CTCL, the median age was 60 years (range, 29-83), and 60% were male. Most had mycosis fungoides (84%), and 16% had Sézary syndrome. The median baseline modified Severity-Weighted Assessment Tool (mSWAT) score was 42.8 (range, 9.7-400). The population was heavily pretreated: 92% of patients had received at least 3 prior lines of therapy, most commonly bexarotene, methotrexate, brentuximab vedotin, and HDAC inhibitors, interferon, topical steroids, radiation, and photopheresis.
What efficacy did ST-001 nanoFenretinide show in CTCL?
Responses tended to emerge early, particularly at the higher dose levels. “If patients are responding, they are responding quite fast,” said Oleg E. Akilov, MD, PhD, an associate professor at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania. He noted that improvement was sometimes visible by the first on-study assessment: “So this is week three, so usually when they come for assessment for a second time, so even after the first infusion, you can see responses in that curve.”
Pharmacokinetic sampling showed that fenretinide reached high concentrations and could be traced in the skin shortly after the end of infusion, and fenretinide Cmax approached approximately 200 µM at higher doses, with an exploratory association with response. Investigators are continuing to refine dosing: “We’re still looking for the magic dose, where we can have good balance between response and tolerability,” Akilov said.
One illustrative case was a patient with stage IVA Sézary syndrome who achieved a PR at 896 mg/m² per day (dose level 11), with a 95.3% reduction in mSWAT, after prior methotrexate, romidepsin, durvalumab (Imfinzi), and mogamulizumab (Poteligeo). The patient came off study in a confirmed PR after completing the maximum 8 cycles. The fenretinide Cmax was 82 µM at the end of infusion on cycle 1, day 1, and a metabolite appeared in the blood by the end of infusion, consistent with rapid tissue delivery.
What did the safety analysis of ST-001 show?
Treatment-related adverse effects (TRAEs) were dose related, with no treatment-related deaths and no cytopenias, sepsis, or cardiac or neurologic toxicity. At 1.25 to 640 mg/m² per day, no significant grade 3 or higher TRAEs occurred except for one grade 3 ulceration over CTCL lesions at 20 mg/m².
At 896 mg/m² per day, single grade 3 events of bone pain, back pain, hypercholesterolemia, and acute kidney injury were reported (n = 1 each). At 1254 mg/m² per day, hypercholesterolemia occurred in 4 patients (grade 4 in 3; grade 3 in 1), along with single grade 3 events of nausea, vomiting, hepatobiliary disorder, and aspartate aminotransferase or alanine aminotransferase increase. Hypercholesterolemia was reversible within the 21-day cycle and was not reported at off-study visits.
Eye-related TRAEs increased with dose, but no grade 3 or higher ocular events occurred; all were grade 1 except for four grade 2 events observed at doses of at least 1254 mg/m². “Patients [experience] ocular issues, but those effects disappear after discontinuation of the drug,” Akilov said. AE-related discontinuations were rare, limited to one consent withdrawal at 1254 mg/m² for grade 2 night blindness.
What are the next steps for ST-001 in CTCL?
Dose level 13 has been completed, and phase 1a enrollment is closed, with 3 patients continuing on treatment. A dose-scheduling study is enrolling into a weekly schedule (dose level 12W) to investigate the safety and clinical activity of weekly dosing.
A phase 1b trial is planned with a 6-month induction, 6 months of weekly maintenance, and a 6-month observation period. The primary end point is stable disease accompanied by pruritus response, confirmed PR, or confirmed CR. The protocol is under review by a central institutional review board (IRB) and local IRBs and is filed under an investigational new drug (IND) application with the FDA.
“It’s going to be induction for 6 months, it’s going to be five days interval, after that we’re going to switch on just weekly, once a week injection, and there’s going to be observation,” Akilov concluded.
Disclosures: Akilov reported serving as a consultant for SciTech Development, Inc. Several coauthors reported employment with, equity ownership in, or consultancy for SciTech Development, Inc.
References
- Akilov OE, Christine Q, Auris H, et al. Preliminary clinical activity of ST-001 nanoFenretinide in previously treated CTCL: first-in-human phase 1a trial results. Presented at: 6th World Congress of Cutaneous Lymphomas; June 25-27, 2026; Montréal, Canada.
- Agar NS, Wedgeworth E, Crichton S, et al. Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol. 2010;28(31):4730-4739. doi:10.1200/JCO.2009.27.7665
- Mohrbacher AM, Yang AS, Groshen S, et al. Phase I study of fenretinide delivered intravenously in patients with relapsed or refractory hematologic malignancies: a California Cancer Consortium trial. Clin Cancer Res. 2017;23(16):4550-4555. doi:10.1158/1078-0432.CCR-17-0234
- Moiin A, Donekal Y, Scarmoutzos L, et al. First-in-human phase 1a clinical trial of the investigational new drug ST-001, a novel nano-phospholipid dispersion formulation of fenretinide, in relapsed/refractory T-cell non-Hodgkin lymphoma. Blood. 2024;144(suppl 1):4453. doi:10.1182/blood-2024-211734
