TCL-139: Safety of Mogamulizumab in Mycosis Fungoides and Sézary Syndrome: Final Results from the Phase 3 MAVORIC Study

Context: MAVORIC was an open-label, multicenter, randomized phase 3 study evaluating the safety and efficacy of mogamulizumab compared to vorinostat in patients with previously treated mycosis fungoides (MF) or Sezary syndrome (SS) ( NCT01728805 ). Primary results have been reported based on a data cutoff date of December 31, 2016 (Kim Y, et al. Lancet Oncol 2018). The most common treatment-emergent adverse events (TEAEs) of any cause reported in patients randomized to mogamulizumab were infusion-related reaction (33.2%), drug eruption (23.9%), diarrhea (23.4%), and fatigue (23.4%). This report provides final safety results as of January 3, 2019. Design: Patients were randomized 1:1 to mogamulizumab 1.0 mg/kg administered intravenously on Days 1, 8, 15, and 22 of the first cycle and on Days 1 and 15 of subsequent cycles or to vorinostat 400 mg administered orally once daily. Patients receiving vorinostat could cross over to mogamulizumab upon progression or intolerable toxicity. Results: In total, 372 patients were randomized (mogamulizumab, 186; vorinostat, 186), and 370 received study drug and were included in the safety analysis (mogamulizumab, 184; vorinostat, 186). Median duration of follow-up was 34.5 months (range, 0.13-70.0) in the randomized part of the study. The type and frequency of all-cause TEAEs in both groups were consistent with those reported in the primary analysis. TEAEs that occurred at a higher frequency in the mogamulizumab vs vorinostat arm included infusion-related reaction (33.2% [61/184] vs 0.5% [1/186], respectively) and drug eruption (25.0% [46/184] vs 1.1% [2/186]); the majority (>80%) of these events were grade 1 or 2. Rates of discontinuation due to AEs were similar between treatment arms and in crossover patients (mogamulizumab, 21.7% [40/184]; vorinostat, 23.7% [44/186]; crossover, 25.9% [35/135]). The median [95% CI] overall survival was similar across treatment groups (57.17 months [43.2, -] for mogamulizumab and 58.37 [45.6, -] for vorinostat, not adjusted for crossover). Conclusions: This final safety analysis from the MAVORIC study in patients with previously treated MF and SS demonstrated that mogamulizumab was generally well tolerated. Longer follow-up and treatment exposure did not identify any new safety signals. Funding: Kyowa Kirin.