In a registrational trial reported in the Journal of Clinical Oncology, Foss et al found that denileukin diftitox (DD)-cxdl—a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2—was active in patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL). DD-cxdl is an improved purity formulation of denileukin diftitox.
Study Details
In the study, 69 patients were enrolled in a primary efficacy analysis set from sites in the United States and Australia. After a dose-finding lead-in, DD-cxdl was given intravenously once daily for 5 days at 9 mg/kg of every 21 days for up to eight cycles. Patients in the primary efficacy analysis set had to have stage IA–IIIB CTCL (mycosis fungoides and/or Sézary syndrome) and at least one previous systemic therapy. The primary outcome measure was objective response rate using the Global Response Score.
Key Findings
Objective response was observed in 25 of 69 patients (36.2%, 95% confidence interval [CI] = 25.0%–48.7%), including 6 (8.7%) with a complete response. An additional 36 patients (52.2%) had stable disease. Median duration of response was 8.9 months (95% CI = 5.0 months to not estimable); median time to response was 1.4 months (95% CI = 0.7-2–1 months). A total of 84.4% of patients had decreased skin tumor burden, with 48.4% having at least a 50% reduction.
Adverse events of special interest, most of which were grade 1 or 2, included infusion reaction (73.9%), hypersensitivity (68.1%), hepatotoxicity (36.2%), and capillary leak syndrome (20.3%). Other common adverse events of any grade included nausea (43.5%) and fatigue (31.9%). Grade ≥ 3 adverse events occurred in 43.5% of patients, most commonly increased alanine aminotransferase (8.7%) and capillary leak syndrome, infusion reaction, and pruritus (5.8% each). Adverse events led to discontinuation of treatment in eight patients (11.6%).
The investigators concluded: “Efficacy and safety results show that DD-cxdl would potentially fulfill a serious, unmet medical need for patients with [relapsed/refractory] CTCL.”
Francine M. Foss, MD, of Yale University School of Medicine, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Citius Pharmaceuticals, Inc. For full disclosures of the study authors, visit ascopubs.org.
