Phase III UNITY-CLL Trial Shows Promise for Umbralisib, Ublituximab Combo in CLL

Positive topline results from the global phase III UNITY-CLL trial evaluating the combination of umbralisib plus ublituximab (U2) compared to obinutuzumab (Gazyva) plus chlorambucil (Leukeran) in patients with previously untreated and relapsed or refractory chronic lymphocytic leukemia (CLL) were announced by TG Therapeutics, the developer of the combination. 

The trial met its primary endpoint at a prespecified interim analysis, demonstrating a statistically significant improvement in progression-free survival (PFS; P< 0.0001), and will be stopped early for superior efficacy. Notably, PFS was assessed by an Independent Review Committee (IRC), and benefit was also observed across both previously untreated and relapsed or 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. Secondary endpoints, including safety, were not reviewed by the DSMB at this meeting.

“It’s extremely gratifying to see positive results for this important trial exploring the combination of umbralisib and ublituximab in patients with both front-line and relapsed/refractory CLL. Today’s outcome marks the first successful phase III trial of a PI3K delta-based regimen in a CLL patient population that included previously untreated patients,” John Gribben, MD, DSc FRCP, FRCPath, FMed Sci, professor of medical oncology at Barts Cancer Institute in London and global study chair for the study, said in a press release. “CLL remains incurable and new treatment options are still very much needed, particularly those that provide a differentiated mechanism and safety profile from our currently available treatment options.”

The phase III UNITY-CLL trial is being conducted under special protocol assessment agreement with the FDA. Further, data from this study is intended to support a regulatory submission targeted by year-end 2020 for U2 in both patients who were previously untreated with CLL and patients with relapsed or refractory CLL and will be submitted for presentation at a future medical conference.

“We are extremely pleased with the performance of U2 in this study and very happy we were able to stop the study at this interim analysis due to the superior efficacy observed,” Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics, said in a press release. We want to thank the patients, their families, and the doctors and research teams who participated in this trial, as well as our extraordinary team at TG who made this study a success. We look forward to submitting this data to the FDA and presenting the full results at a major medical meeting targeted by year-end 2020.”

Participants in the trial were randomized into 4 arms, including ublituximab single agent, umbralisib single agent, ublituximab plus umbralisib, and an active control arm of obinutuzumab plus chlorambucil. Moreover, a prespecified analysis was conducted to evaluate the contribution of ublituximab and umbralisib in the U2 combination arm and allowed for the termination of the single agent arms.

Thereafter, the phase III UNITY-CLL trial continued enrollment in a 1:1 ratio into the 2 combination arms. Full enrollment into the phase III UNITY-CLL trial was complete in October 2017, with approximately 420 individuals enrolled in the 2 combination arms. Further, the trial enrolled approximately 60% patients with treatment naïve CLL and 40% with relapsed or refractory CLL. 

Reference:

TG Therapeutics Announces Positive Topline Results from the UNITY-CLL Phase 3 Study Evaluating the Combination of Umbralisib and Ublituximab (U2) for the Treatment of Patients with Chronic Lymphocytic Leukemia [news release]. New York. Published May 5, 2020. ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-announces-positive-topline-results-unity-cll. Accessed May 5, 2020.