Background:Cutaneous T-cell lymphoma (CTCL) is a rare, incurable non-Hodgkin lymphoma characterized by immune dysregulation and chronic skin inflammation. Interferon-α has demonstrated activity in CTCL with response rates of 30–80%, but its use is limited by short half-life, frequent dosing, and toxicities. Pegylated IFN-α2a (Pegasys) is widely used, but recent U.S. shortages have created a treatment gap. Ropeginterferon alfa-2b (P1101), a monopegylated IFN-α2b with longer half-life and improved pharmacokinetics, is FDA-approved for polycythemia vera but has not been studied in CTCL. This trial evaluates P1101 to define the recommended Phase 2 dose (RP2D) and explore immune correlates.
Methods:This is a single-center, open-label Phase I/Ib investigator-initiated trial (NCT07047885). Eligible patients have stage IA–IIIB CTCL without large cell transformation and inadequate response to ≥2 lines of skin-directed therapy or systemic modalities. The Phase I dose-escalation cohort (up to 18 patients) employs a Bayesian Optimal Interval design at 250, 350, and 500 mcg administered subcutaneously every 2 weeks, with intra-patient titration allowed. Dose-limiting toxicities (DLTs) are defined by CTCAE v5.0, with Bayesian continuous monitoring to ensure safety. An expansion cohort (up to 20 patients) will further assess safety, efficacy (mSWAT, PROs), and biomarker modulation.
Results:Enrollment is ongoing. Correlative studies include serial blood and skin sampling to evaluate immune cell subsets, cytokines, and gene expression as predictors of response.
Conclusions:This is the first study of ropeginterferon in CTCL in the U.S. and will establish the RP2D, safety profile, and immune effects of sustained interferon therapy in this population.
