Advanced Follicular Lymphoma Patients Show Positive Overall Response to Umbralisib in Phase 2 Trial

TG Therapeutics’ umbralisib (TGR-1202), an inhibitor of the PI3K delta protein, has shown promising response rates in patients with relapsed or refractory follicular lymphoma, according to new data from a Phase 2b clinical trial.

The UNITY-NHL trial (NCT02793583) included 118 follicular lymphoma patients previously treated with at least two lines of therapy, including an anti-CD20 regimen and an alkylating agent.

According to the company, the overall response rate (ORR) was above the established threshold of 40%, with the trial meeting its primary goal. Use of umbralisib was also well-tolerated, with a safety profile similar to other trials.

TG Therapeutics plans to submit additional UNITY-NHL’s results for presentation at a future medical meeting, and to share them with the U.S. Food and Drug Administration.

“There are no fully approved drugs for patients with follicular lymphoma that have progressed following two or more prior lines of therapy and we are excited by the potential to offer a novel treatment for this underserved population,” Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics, said in a press release.

“We are extremely pleased to announce that the UNITY-NHL follicular lymphoma cohort [patient group] evaluating umbralisib monotherapy met the primary endpoint of ORR,” added Weiss. “We look forward to sharing these results with the FDA and discussing submission opportunities for accelerated approval of umbralisib in follicular lymphoma.”

Umbralisib is an oral inhibitor of PI3K delta, a family of proteins that play important roles in the growth and survival of immune B-cells, which are implicated in different types of lymphoma, including follicular lymphoma.

The ongoing UNITY-NHL trial (NCT02793583) is testing umbralisib, alone or in combination with other treatments, in non-Hodgkin’s lymphoma patients who failed to respond to at least one prior line of therapy and are not candidates for high-dose chemotherapy and a stem cell transplant.

The trial is expected to enroll 900 patients with several lymphoma types, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma. They are being randomized to one of three groups: umbralisib alone; umbralisib in combination with ublituximab (an anti-CD20 antibody under development by the company); or umbralisib plus ublituximab and the chemotherapy bendamustine.

In addition to the benefits seen in the follicular lymphoma group, TG Therapeutics has presented data from the marginal zone lymphoma patients given umbralisib alone. Among the 42 patients treated to date — all of whom had failed to respond to prior CD20 targeted therapy — 52% responded to umbralisib, and an additional 36% attained stable disease, for a clinical benefit rate of 88%.

Based on these findings, the FDA gave umbralisib breakthrough therapy status for the treatment of adults patients with marginal zone lymphoma. TG Therapeutics is planning to pursue accelerated approval for this indication.

Umbralisib is also being evaluated in the UNITY-CLL Phase 3 trial (NCT02612311) in combination ublituximab, in both untreated and in previously treated chronic lymphocytic leukemia (CLL) patients.

“These are very exciting times for TG and with two additional major events targeted to occur over the next several months, including commencing our first NDA [new drug application] filing for umbralisib in patients with relapsed/refractory marginal zone lymphoma and results from our UNITY-CLL Phase 3 trial, we expect that excitement to continue,” Weiss said.

“Taken together, we see 2020 shaping up as a pivotal year where we transition from a development-stage company into a fully-integrated development and commercial organization,” he added.