Umbralisib Monotherapy Reaches ORR End Point in Follicular Lymphoma Population of Pivotal NHL Trial

Umbralisib (TGR-1202) monotherapy demonstrated positive responses in patients with previously treated follicular lymphoma, meeting the primary end point for the follicular lymphoma cohort of the phase IIb UNITY-NHL trial, TG Therapeutics announced in a press release.¹

The single-agent PI3K-delta inhibitor surpassed the prespecified target of an objective response rate (ORR) of at least 40% to 50% in patients with follicular lymphoma who have received at least 2 prior treatment regimens, including an anti-CD20 monoclonal antibody and an alkylating agent.

Further data from the follicular lymphoma cohort are expected to be presented at a future medical meeting and discussed with the FDA.

“We are extremely pleased to announce that the UNITY-NHL follicular lymphoma cohort evaluating umbralisib monotherapy met the primary endpoint of ORR,” Michael S. Weiss, executive chairman and CEO of TG Therapeutics, stated in a press release. “There are no fully approved drugs for patients with follicular lymphoma that have progressed following 2 or more prior lines of therapy and we are excited by the potential to offer a novel treatment for this underserved population. We look forward to sharing these results with the FDA and discussing submission opportunities for accelerated approval of umbralisib in follicular lymphoma."

The pivotal phase IIb UNITY-NHL trial is a multicenter, open-label, multicohort study that is investigating the use of umbralisib as both a single agent and as part of combination regimens in patients with non-Hodgkin lymphomas (NCT02793583). Patients with relapsed or refractory, transplant-ineligible diffuse large B-cell lymphoma, follicular lymphomas, mantle cell lymphoma, or marginal zone lymphoma (MZL) with an ECOG performance status of 0 to 2 are eligible for enrollment in one of the study cohorts.

The follicular lymphoma cohort is looking at the safety and efficacy of umbralisib in patients with follicular lymphoma who have previously received at least 2 prior lines of therapy. The primary end point is ORR by independent review committee assessment and secondary end points include safety, duration of response (DOR), and progression-free survival (PFS).

ORR findings were based on responses in 118 patients with follicular lymphoma who had received at least 1 dose of umbralisib. The monotherapy appeared to be well tolerated in this patient population with a safety profile that was consistent with previous reports for the PI3K inhibitor.

“These are very exciting times for TG and with 2 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 III trial, we expect that excitement to continue,” Weiss added in the press release.

Previous reports from the MZL cohort demonstrated the efficacy of umbralisib monotherapy in patients with relapsed/refractory MZL.²

The MZL cohort included patients with MZL who had previously received at least 1 prior line of treatment including at least 1 anti-CD20 monoclonal antibody—containing regimen.

Of 69 enrolled patients, data presented at the 2019 ASCO Annual Meeting covered 38 eligible patients who had been followed for at least 6 months as of the data cutoff (median, 9.6 months). These patients received 800 mg umbralisib once daily until progressive disease or unacceptable toxicity.

The median age of the eligible patients was 67 years (range, 34-81) and they had received a median of 2 prior systemic treatments (range, 1-5).

The ORR was 55%, consisting of 4 complete responses and 17 partial responses. Additionally, 11 patients (29%) achieved stable disease, with 6 of these patients still on treatment as of data cutoff. Overall, 58% of patients continued on treatment as of the data cutoff. The clinical benefit rate was 84% and tumor reductions were seen in 91% of patients.

The median time to response was 2.7 months and the median DOR was not reached. The PFS rate at 1 year was 71%.

Common (≥20%) adverse events (AEs) of any grade included diarrhea (45%), nausea (29%), fatigue (26%), headache (26%), cough (24%), and decreased appetite (21%). The most common grade 3/4 AEs were neutropenia (8%), febrile neutropenia (5%), and diarrhea (5%).

References

1. TG Therapeutics Announces Positive Results from the UNITY-NHL Phase 2b Pivotal Trial Evaluating Umbralisib Monotherapy in Patients with Relapsed/Refractory Follicular Lymphoma [press release]. New York: TG Therapeutics, Inc; October 28, 2019. https://bit.ly/2JOU8Yn. Accessed October 30, 2019.
2. Fowler NH, Samaniego F, Jurczak W, et al. Umbralisib monotherapy demonstrates efficacy and safety in patients with relapsed/refractory marginal zone lymphoma: A multicenter, open label, registration directed phase II study.J Clin Oncol. 2019;37(suppl 15; abstr 7506). doi: 10.1200/JCO.2019.37.15_suppl.7506.