TG Therapeutics announced positive topline results from the global UNITY-CLL Phase 3 trial evaluating the combination of umbralisib plus ublituximab (U2) compared to obinutuzumab plus chlorambucil in patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia (CLL). The trial met its primary endpoint at a prespecified interim analysis demonstrating a statistically significant improvement in progression-free survival (PFS) and will be stopped early for superior efficacy. PFS was assessed by an Independent Review Committee (IRC), and benefit was also seen across both previously untreated and relapsed/refractory patient populations. An independent data safety monitoring board (DSMB) conducted the interim analysis and made the recommendation to stop the trial early based on the positive results.
The UNITY-CLL Phase 3 trial is being conducted under Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA). Data from this study is intended to support a regulatory submission targeted by year-end 2020 for U2 in both previously untreated and relapsed/refractory CLL patients and will be submitted for presentation at a future medical conference.
UNITY-CLL is a global randomized controlled clinical trial comparing the combination of ublituximab plus umbralisib, or U2, to an active control arm of obinutuzumab plus chlorambucil in patients with both treatment-naïve and relapsed or refractory chronic lymphocytic leukemia (CLL). The trial randomized patients into four treatment arms: ublituximab single agent, umbralisib single agent, ublituximab plus umbralisib and an active control arm of obinutuzumab plus chlorambucil. A prespecified analysis was conducted to assess the contribution of ublituximab and umbralisib in the U2 combination arm and allowed for the termination of the single agent arms. Accordingly, the UNITY-CLL Phase 3 trial continued enrollment in a 1:1 ratio into the two combination arms: the investigational arm of U2 and the control arm of obinutuzumab plus chlorambucil. Full enrollment into the UNITY-CLL Phase 3 trial completed in October of 2017 with approximately 420 subjects enrolled to the two combinations arms. This trial enrolled approximately 60% treatment-naïve CLL patients and 40% relapsed or refractory CLL patients. The primary endpoint for this study was superior Progression Free Survival (PFS) for the U2 combination compared to the control arm to support the submission for full approval of the U2 combination in CLL.
About umbralisib plus ublituximab
Ublituximab (TG-1101) is a novel, glycoengineered monoclonal antibody that targets a specific and unique epitope on the CD20 antigen found on mature B-lymphocytes. Umbralisib (TGR-1202) is an oral, once-daily dual inhibitor of PI3K-delta and CK1-epsilon, which may lead to a differentiated safety profile.