MAVORIC trial of Poteligeo consistent with safety data in cutaneous T-cell lymphoma.- Kyowa Kirin

Kyowa Kirin announced the final safety data from the MAVORIC trial of Poteligeo (mogamulizumab-kpkc), in cutaneous T-cell lymphoma (CTCL). MAVORIC is the first pivotal trial in CTCL to use progression-free survival (PFS) as a primary endpoint. It is also the largest randomized study to compare systemic therapies in subtypes of CTCL. Secondary endpoints included a proportion of patients achieving an overall response rate (ORR), duration of response and safety. Primary results were based on a data cutoff of December 31, 2016, which served as the basis of the FDA and EMA approvals of mogamulizumab for the treatment of the most common subtypes of CTCL as well as a partial change of the product label in Japan. The analysis being presented at TCLF reports final safety results of MAVORIC as of the safety data available on January 3, 2019, based on patients who continued participating in the trial post-approval. For the final safety analysis, median duration of follow-up was 34.5 months (range, 0.13-70.0). Median treatment exposure was 170 days (range, 1-1813) for mogamulizumab and 84 days for vorinostat, which represent the same median values but broader ranges compared to the primary analysis (primary analysis, 170 days [1-1379] for mogamulizumab and 84 days [4-1058] for vorinostat). This final safety analysis from the MAVORIC study in patients with previously treated mycosis fungoides (MF) and Sézary syndrome (SS) demonstrated that mogamulizumab did not identify any new safety signals. The type and frequency of adverse events (AEs) in either the mogamulizumab or vorinostat treatment groups were consistent with those reported in the primary analysis. Treatment-emergent adverse events (TEAEs), regardless of causality, were reported at similar rates in the two treatment groups and included constipation, peripheral edema, headache, and anemia. TEAEs that occurred at higher frequency in the mogamulizumab vs. vorinostat arm included infusion-related reaction (33.2% vs 0.5%) and drug eruption (25.0% vs 1.1%). The majority of these events were grade 1 or 2, and the types and frequencies of AEs attributable to mogamulizumab included infusion-related reaction (33.2% [61/184]), drug eruption (23.9% [44/184]), and fatigue (18.5% [34/184]). AEs attributed to vorinostat included diarrhea (55.4% [103/186]), nausea (38.2% [71/186]), and fatigue (33.3% [62/186]). In the trial, patients on vorinostat for at least two cycles who demonstrated confirmed disease progression or experienced intolerable toxicity (grade =>3 adverse events [AEs], excluding inadequately treated nausea, vomiting, and diarrhea; and alopecia), despite dose reduction and appropriate management of side effects, could cross over to treatment with mogamulizumab. This analysis confirmed earlier findings showing that the type and incidence of TEAEs among patients receiving mogamulizumab after crossover were similar to those observed for patients initially randomized to mogamulizumab. Data will be presented at the 12th Annual T-Cell Lymphoma Forum (TCLF) in La Jolla, California.