FDA Fast Tracks Combination Therapy for Chronic Lymphocytic Leukemia

The FDA has granted a fast track designation to the investigational CD20-directed monoclonal antibody ublituximab in combination with the PI3K-delta inhibitor umbralisib (U2 regimen) for the treatment of adult patients with chronic lymphocytic leukemia (CLL).¹

Positive topline results of the combination were unveiled in May 2020 from the phase 3 UNITY-CLL trial, in which the doublet improved progression-free survival (PFS) compared with obinutuzumab (Gazyva) plus chlorambucil in patients with previously untreated and relapsed/refractory disease.² The study is being conducted under a Special Protocol Assessment agreement with the FDA. An independent review panel determined that the chemotherapy-free U2 combination induced a statistically significant improvement in PFS (P < .0001), and the panel recommended that the trial be stopped early.

"We are extremely pleased to have received fast track designation for the ublituximab plus umbralisib regimen, or the U2 combination, to treat adult patients with CLL. The application for Fast Track was based on data from the UNITY-CLL phase 3 study that we announced earlier this year had met its primary endpoint of progression free survival,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics, the developer of both agents.

In the phase 3 UNITY-CLL trial, patients with both treatment-naïve and relapsed/refractory CLL were initially randomized into 1 of 4 treatment arms: single-agent ublituximab; single-agent umbralisib; U2; or obinutuzumab plus chlorambucil. The trial design did allow for discontinuation of the 2 monotherapy arms following a positive assessment of the U2 combination. Randomization, at that point, continued with the U2 and obinutuzumab/chlorambucil arms only.

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