The FDA granted priority review to a biologics license application (BLA) for the anti-CCR4 monoclonal antibody mogamulizumab for patients with cutaneous T-cell lymphoma (CTCL) who have received at least one prior systemic therapy.
The BLA is based on findings from the phase III MAVORIC study, which demonstrated that mogamulizumab reduced the risk of disease progression or death by 47 percent, compared with vorinostat in patients with previously treated CTCL. The study included 372 people with histologically confirmed mycosis fungoides or SÃ©zary syndrome (two subtypes of CTCL) that had not responded to at least one systemic therapy. Patients were randomized 1:1 to receive mogamulizumab 1.0 mg/kg weekly for the first month, then every two weeks (n=186; median age = 63.5 years; range = 25-101 years), or vorinostat 400 mg daily (n=186; median age = 65.0 years; range = 25-89 years). Patients receiving vorinostat whose disease progressed or had intolerable toxicity were permitted to crossover to the mogamulizumab cohort.
Median PFS was 7.7 months in the mogamulizumab arm (range = 5.7-10.3 months), compared with 3.1 months in the vorinostat arm (range=2.9-4.1 months; HR=0.53; 95% CI 0.41-0.69; p<0.0001). The PFS benefit with mogamulizumab was observed across predefined subgroups, including disease type and disease stage.
The overall response rate (ORR) was 28 percent with mogamulizumab versus 4.8 percent with vorinostat (p<0.0001).
Grade 1/2 treatment-related AEs were reported by 54.9 percent of patients receiving mogamulizumab, and 42.4 percent experienced grade 3-5 AEs. The most common AEs (occurring in >20% of patients) associated with mogamulizumab and vorinostat included infusion-related reactions (33.2% vs. 0.5%) and skin eruptions (23.9% vs. 0.5%).
Sources: Kyowa Hakko Kirin press release, November 28, 2017; Kim YH, Bagot M, Pinter-Brown L, et al. Anti-CCR4 monoclonal antibody, mogamulizumab, demonstrates significant improvement in PFS compared to vorinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL): results from the phase III MAVORIC study. Abstract #817. Presented at the 2017 American Society of Hematology Annual Meeting, December 11, 2017; Atlanta, GA.