Youn H. Kim, MD
The anti-CCR4 monoclonal antibody mogamulizumab reduced the risk of progression or death by 47% compared with vorinostat (Zolinza) in previously treated patients with cutaneous T-cell lymphoma (CTCL), according to findings from the phase III MAVORIC study presented at the 2017 ASH Annual Meeting.
Late last month, the FDA granted a priority review to a biologics license application (BLA) for mogamulizumab for the treatment of patients with CTCL who have received at least 1 prior systemic therapy. Under the Prescription Drug User Fee Act, the FDA is scheduled to make its final decision on the BLA by June 4, 2018.
“This is the first report of a randomized phase III study evaluating progression-free survival (PFS) as a primary endpoint in CTCL to compare a new systemic therapy against an FDA-approved agent, utilizing the consensus comprehensive global response criteria,” lead study author Youn H. Kim, MD, a professor of Dermatology and member of the Stanford Cancer Institute, said when presenting the findings at ASH.
“Mogamulizumab, a novel CCR4-targeting antibody therapy, demonstrated significantly superior efficacy outcomes compared to vorinostat in patients with previously treated CTCL,” added Kim.
The MAVORIC study included 372 patients with histologically confirmed stage IB to IVB mycosis fungoides (MF) or Sézary syndrome (SS; two subtypes of CTCL) who had failed ≥1 systemic therapy. Patients were evenly randomized to 1.0 mg/kg of mogamulizumab weekly for the first 4-week cycle and then every 2 weeks, or vorinostat at 400 mg daily. Crossover to mogamulizumab was allowed for patients receiving vorinostat who progressed or had intolerable toxicity. PFS was the primary endpoint.
Patient characteristics were similar between the 2 arms. These included age (median, 63.5 vs 65 years in the mogamulizumab vs vorinostat arms, respectively), ECOG performance status of 0 or 1 (99% vs 100%), and stage III/IV disease (63.4% vs 61.3%). In both arms, the median number of prior systemic therapies was 3. CCR4 expression level was not an eligibility criteria.
The investigator-assessed median PFS was 7.7 months (95% CI, 5.7-10.3) in the mogamulizumab arm compared with 3.1 months (95% CI, 2.9-4.1) in the vorinostat arm (hazard ratio [HR], 0.53; 95% CI, 0.41-0.69; P
<.0001). By independent review, the median PFS was 6.7 versus 3.8 months, respectively (HR, 0.64; 95% CI, 0.49-0.84; P
= .0007). The PFS benefit with mogamulizumab was observed across predefined subgroups, including disease type and disease stage.
The overall response rate (ORR) was 28% with mogamulizumab versus 4.8% with vorinostat (P
<.0001). Among patients with MF and SS, the ORR was 21.0% vs 7.1% (P
= .0042) and 37.0% vs 2.3% (P
<.0001), respectively. Mogamulizumab also improved ORR in patients with stage III disease at 22.7% versus 0, and stage IV disease at 36.5% versus 3.1%. Among patients assigned to vorinostat who crossed over to mogamulizumab, the ORR was 30.1%
“These are confirmed global composite responses of all the compartments—skin, lymph node, blood, etc—they are all integrated into this response criteria. So, it’s not just skin response,” said Kim.
Grade 1/2 treatment-emergent adverse events (TEAEs) were experienced by 54.9% of patients receiving mogamulizumab, with 42.4% of patients experiencing grade 3 to 5 TEAEs.
TEAEs occurring in more than 20% of patients that were more common with mogamulizumab versus vorinostat included infusion-related reactions (33.2% vs 0.5%) and skin eruptions due to drug (23.9% vs 0.5%).
TEAEs more common with vorinostat versus mogamulizumab included diarrhea (61.8% vs 23.4%), nausea (42.5% vs 15.2%), thrombocytopenia (30.6% vs 11.4%), dysgeusia (29.0% vs 3.3%), and increased blood creatinine (28.0% vs 3.3%).
Kim also noted that, “Patient-reported outcomes (Skindex-29 and FACT-G) demonstrated significant improvement with mogamulizumab.”
“We are very excited and we hope that this drug will be approved [by the FDA] early next year to add to the limited options that we have in our [CTCL] patient population,” concluded Kim.
Kim YH, MD, 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 available ahead of 2017 ASH Annual Meeting; December 9-12, 2017; Atlanta, GA. Abstract 817.