Zanolimumab, a Fully Human Monoclonal Antibody: Early Results of an Ongoing Clinical Trial in Patients with CD4⁺ Mycosis Fungoides (MF) Type CTCL (Stage IB-IVB) Who Are Refractory or Intolerant to Targretin and One Other Standard Therapy.

Zanolimumab (previously referred to as HuMax-CD4) is a fully human monoclonal IgG1k antibody, targeting the CD4 molecule on T-cells. It exhibits cytotoxic and anti-proliferative effects and has previously shown efficacy in cutaneous T-cell lymphoma. We report the early safety and peripheral CD4⁺ cell depletion results from the open-label, dose escalation part of a US phase III efficacy study. So far, 21 patients have been recruited and the results from the 4 mg/kg dose group (9 patients) and 8 mg/kg dose group (6 patients) are available. Zanolimumab was administered iv, once weekly for 12 weeks. In total, 2 Serious Adverse Events have been reported. Of these, 1 case of large cell transformation in a patient with large cells present prior to inclusion was judged possibly related to treatment by investigator. No increase in toxicity was seen upon dose escalation. Marked depletion of CD4⁺ T-cells was observed after just 1 infusion of zanolimumab at both dose levels. One week following the last dose, the median (range) peripheral blood CD4+ T-cell count compared to baseline values was decreased from 831 per μL (167–1928) to 24 per μL (4–141) in 4 mg/kg dose-group and from 638 per μL (182–1024) to 9 per μL (4–19) in the 8 mg/kg dose-group. These initial data indicate that zanolimumab has an acceptable tolerability profile at the doses tested and results in a rapid and pronounced decrease in peripheral CD4⁺ counts in MF CTCL patients.